Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| the human carnitine transporter slc22a16 mediates high affinity uptake of the anticancer polyamine analogue bleomycin-a5. | bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. however, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. previously, we documented that the saccharomyces cerevisiae l-carnitine transporter agp2 is responsible for the high affinity uptake of polyamines and of the polyamine an ... | 2010 | 20037140 |
| mtor binds to the promoters of rna polymerase i- and iii-transcribed genes. | target of rapamycin (tor) is a conserved regulator of gene expression from yeast to humans. in budding yeast, tor is associated with ribosomal dna (rdna) promoter, which is critical for ribosome biogenesis and transfer rna (trna) synthesis. whether mtor behaves similarly in mammalian cells is unknown. here, we report that mtor is detected at several different promoters in human and murine cells, including that of rdna and trna genes. the association of mtor with these promoters is regulated by g ... | 2010 | 20038818 |
| appl1 is dispensable for mouse development, and loss of appl1 has growth factor-selective effects on akt signaling in murine embryonic fibroblasts. | the adaptor protein appl1 (adaptor protein containing pleckstrin homology (ph), phosphotyrosine binding (ptb), and leucine zipper motifs) was first identified as a binding protein of akt2 by yeast two-hybrid screening. appl1 was subsequently found to bind to several membrane-bound receptors and was implicated in their signal transduction through akt and/or mapk pathways. to determine the unambiguous role of appl1 in vivo, we generated appl1 knock-out mice. here we report that appl1 knock-out mic ... | 2010 | 20040596 |
| cell-penetrating dna-binding protein as a safe and efficient naked dna delivery carrier in vitro and in vivo. | non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. using the novel, human-origin hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked dna in vitro and in vivo. the new dna delivery system contains hph-1-gal4 dna-binding domain (dbd) fusion protein and enhanced green fluorescent protein (egfp ... | 2010 | 20043881 |
| structure of trypanosoma brucei glutathione synthetase: domain and loop alterations in the catalytic cycle of a highly conserved enzyme. | glutathione synthetase catalyses the synthesis of the low molecular mass thiol glutathione from l-gamma-glutamyl-l-cysteine and glycine. we report the crystal structure of the dimeric enzyme from trypanosoma brucei in complex with the product glutathione. the enzyme belongs to the atp-grasp family, a group of enzymes known to undergo conformational changes upon ligand binding. the t. brucei enzyme crystal structure presents two dimers in the asymmetric unit. the structure reveals variability in ... | 2010 | 20045436 |
| the parl family of mitochondrial rhomboid proteases. | rhomboids are an ancient and conserved family of intramembrane-cleaving proteases, a small group of proteolytic enzymes capable of hydrolyzing a peptide bond within a transmembrane helix that anchors a substrate protein to the membrane. mitochondrial rhomboids evolved in eukaryotes to coordinate a critical aspect of cell biology, the regulation of mitochondrial membranes dynamics. this function appears to have required the emergence of a structural feature that is unique among all other rhomboid ... | 2010 | 20045481 |
| antifungals: need to search for a new molecular target. | in the 1990s, drug resistance has become an important problem in a variety of infectious diseases including human immunodeficiency virus infection, tuberculosis, and other bacterial infections which have profound effects on human health. at the same time, there have been dramatic increase in the incidence of fungal infections, which are probably the result of alterations in immune status associated with the acquired immuno deficiency syndrome epidemic, cancer chemotherapy, and organ and bone mar ... | 2008 | 20046765 |
| it's the data! | three articles from the early years of molecular biology of the cell (mboc) have had remarkably many citations in the literature since their publication approximately 10 years ago. as a coauthor of these articles and the former editor of mboc, i was asked for possible explanations. i believe the answer lies in the unusual nature of these articles: each presents and summarizes gene expression data for nearly every gene in the yeast or human genomes. continuing interest in the data themselves by c ... | 2010 | 20048255 |
| c20orf20 (mrg-binding protein) as a potential therapeutic target for colorectal cancer. | colorectal cancer is one of the most common causes of cancer death worldwide. using cdna microarray containing 23 040 genes, we earlier investigated gene-expression profiles in 11 colorectal cancers for the purpose of better understanding of colorectal carcinogenesis as well as development of novel diagnostic and therapeutic strategies. mrg-binding protein (mrgbp) or c20orf20, encoding a subunit of trrap/tip60-containing histone acetyltransferase complex, was up-regulated in the majority of colo ... | 2010 | 20051959 |
| dna resection in eukaryotes: deciding how to fix the break. | dna double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. dna-end resection, the first step in recombination, is a key step that contributes to the choice of dsb repair. resection, an evolutionarily conserved process that generates single-stranded dna, is linked to checkpoint activation and is critical for survival. failure to regulate and execute this process results in defective recombination and can contribute to human dis ... | 2010 | 20051983 |
| model-guided mutagenesis drives functional studies of human nha2, implicated in hypertension. | human nha2 is a poorly characterized na(+)/h(+) antiporter recently implicated in essential hypertension. we used a range of computational tools and evolutionary conservation analysis to build and validate a three-dimensional model of nha2 based on the crystal structure of a distantly related bacterial transporter, nhaa. the model guided mutagenic evaluation of transport function, ion selectivity, and ph dependence of nha2 by phenotype screening in yeast. we describe a cluster of essential, high ... | 2010 | 20053353 |
| obese and anorexic yeasts: experimental models to understand the metabolic syndrome and lipotoxicity. | lipotoxicity is the pathological consequence of lipid overflow in non-adipose tissue, mediated through reactive lipid moieties which may even lead to lipid-induced cell death (lipoapoptosis). this derailment of cellular and organismal fat homeostasis is the consequence of obesity due to continued over-feeding, and contributes substantially to the pathogenesis of insulin resistance, type 2 diabetes mellitus and cardiovascular disease, which are all components of the metabolic syndrome. now, does ... | 2010 | 20056167 |
| glutaredoxin participates in the reduction of peroxides by the mitochondrial 1-cys peroxiredoxin in saccharomyces cerevisiae. | the mechanism for regeneration of the active-site "peroxidatic" cysteine in 1-cys peroxiredoxins is a matter of debate. saccharomyces cerevisiae prx1 is a mitochondrial enzyme belonging to the 1-cys prx, whereas grx2 is involved in antioxidant defense and localizes at the mitochondria, so we hypothesized that it could be a perfect candidate to resolve the sulfenate in prx1 with gsh. in vitro experiments with purified prx1p and grx2p demonstrate that grx2p, at concentrations <1 microm, coupled to ... | 2010 | 20059400 |
| expression of a foreign epitope on infectious pancreatic necrosis virus vp2 capsid protein subviral particle (svp) and immunogenicity in rainbow trout. | infectious pancreatic necrosis virus (ipnv) is a major viral pathogen of salmonid fish and causes serious economic losses to salmonid aquaculture. previously, we demonstrated that the ipnv capsid protein, vp2, expressed in yeast self-assembles into subviral particles (svps) and injection of these ipnv rvp2 svps into rainbow trout elicits an immune response. immunized fish had reduced viral loads compared to unimmunized fish when challenged with ipnv. to evaluate the suitability of ipnv rvp2 svps ... | 2010 | 20060858 |
| deletion of candida albicans spt6 is not lethal but results in defective hyphal growth. | as a means to study surface proteins involved in the yeast to hypha transition, human monoclonal antibody fragments (single-chain variable fragments, scfv) have been generated that bind to antigens expressed on the surface of candida albicans yeast and/or hyphae. a cdna expression library was constructed from hyphae, and screened for immunoreactivity with scfv5 as a means to identify its cognate antigen. a reactive clone contained the 3' end of the c. albicans gene, orf 19.7136, designated spt6 ... | 2010 | 20060921 |
| expression and purification of recombinant human inward rectifier k+ (kcnj) channels in saccharomyces cerevisiae. | the inward rectifier family of potassium (kcnj) channels regulate vital cellular processes including cell volume, electrical excitability, and insulin secretion. dysfunction of different isoforms have been linked to numerous diseases including bartter's, andersen-tawil, smith-magenis syndromes, type ii diabetes mellitus, and epilepsy, making them important targets for therapeutic intervention. using a family-based approach, we succeeded in expressing 10 of 11 human kcnj channels tested in saccha ... | 2010 | 20064617 |
| structure and function of polarity-inducing kinase family mark/par-1 within the branch of ampk/snf1-related kinases. | kinases of the mark/par-1 family of s/t protein kinases are regulators of diverse cellular processes in caenorhabditis elegans, drosophila, yeast, and mammalian cells. they are involved in nematode embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. mark phosphorylates microtubule-associated proteins such as tau and is a key regulator of microtubule-based intracellular transport. hyperphosphorylation of tau causes defects in neuronal transport and may induc ... | 2010 | 20071654 |
| the sla2p/hip1/hip1r family: similar structure, similar function in endocytosis? | hip1 (huntingtin interacting protein 1) has two close relatives: hip1r (hip1-related) and yeast sla2p. all three members of the family have a conserved domain structure, suggesting a common function. over the past decade, a number of studies have characterized these proteins using a combination of biochemical, imaging, structural and genetic techniques. these studies provide valuable information on binding partners, structure and dynamics of hip1/hip1r/sla2p. in general, all suggest a role in cm ... | 2010 | 20074057 |
| in silico and biological survey of transcription-associated proteins implicated in the transcriptional machinery during the erythrocytic development of plasmodium falciparum. | malaria is the most important parasitic disease in the world with approximately two million people dying every year, mostly due to plasmodium falciparum infection. during its complex life cycle in the anopheles vector and human host, the parasite requires the coordinated and modulated expression of diverse sets of genes involved in epigenetic, transcriptional and post-transcriptional regulation. however, despite the availability of the complete sequence of the plasmodium falciparum genome, we ar ... | 2010 | 20078850 |
| ageing and eating. | epidemiological studies propose that extension of the human lifespan or the reduction of age associated diseases may be achieved by physical exercise, caloric restriction, and by consumption of certain substances such as resveratrol, selenium, flavonoids, zinc, omega 3 unsaturated fatty acids, vitamins e and c, ginkgobiloba extracts, aspirin, green tea catechins, antioxidants in general, and even by light caffeine or alcohol consumption. though intriguing, these studies only show correlative (no ... | 2010 | 20079384 |
| expression of zebrafish (danio rerio) monoamine oxidase (mao) in pichia pastoris: purification and comparison with human mao a and mao b. | the expression, purification and characterization of zebrafish monoamine oxidase (zmao) using the methylotropic yeast pichia pastoris expression system is described. a 1l fermentation culture of pichia pastoris containing the gene encoding zmao under control of the methanol oxidase promotor expresses approximately 200mg of zmao exhibiting 300 u of total activity. the enzyme is found in the mitochondrial fraction of the expression host and is purified in a 30% yield as a homogenous species with a ... | 2010 | 20079438 |
| a severe human metabolic disease caused by deficiency of the endoplasmatic mannosyltransferase halg11 leads to congenital disorder of glycosylation-ip. | a new type of congenital disorders of glycosylation, designated cdg-ip, is caused by the deficiency of gdp-man:man3glcnac2-pp-dolichol-alpha1,2-mannosyltransferase, encoded by the human ortholog of alg11 from yeast. the patient presented with a multisystemic disorder characterized by muscular hypotonia, seizures, developmental retardation and death at the age of 2 years. the isoelectric focusing pattern of the patient's serum transferrin showed the partial loss of complete n-glycan side chains, ... | 2010 | 20080937 |
| identification of inhibitors of plasmodium falciparum phosphoethanolamine methyltransferase using an enzyme-coupled transmethylation assay. | the phosphoethanolamine methyltransferase, pfpmt, of the human malaria parasite plasmodium falciparum, a member of a newly identified family of phosphoethanolamine methyltransferases (pmt) found solely in some protozoa, nematodes, frogs, and plants, is involved in the synthesis of the major membrane phospholipid, phosphatidylcholine. pmt enzymes catalyze a three-step s-adenosylmethionine-dependent methylation of the nitrogen atom of phosphoethanolamine to form phosphocholine. in p. falciparum, t ... | 2010 | 20085640 |
| mir-17, mir-19b, mir-20a, and mir-106a are down-regulated in human aging. | aging is a multifactorial process where deterioration of body functions is driven by stochastic damage while counteracted by distinct genetically encoded repair systems. to better understand the genetic component of aging, many studies have addressed the gene and protein expression profiles of various aging model systems engaging different organisms from yeast to human. the recently identified small non-coding mirnas are potent post-transcriptional regulators that can modify the expression of up ... | 2010 | 20089119 |
| bicaudal d1-dependent trafficking of human cytomegalovirus tegument protein pp150 in virus-infected cells. | human cytomegalovirus (hcmv) virion assembly takes place in the nucleus and cytoplasm of infected cells. the hcmv virion tegument protein pp150 (ppul32) is an essential protein of hcmv and has been suggested to play a role in the cytoplasmic phase of hcmv assembly. to further define its role in viral assembly and to identify host cell proteins that interact with pp150 during viral assembly, we utilized yeast two-hybrid analyses to detect an interaction between pp150 and bicaudal d1 (bicd1), a pr ... | 2010 | 20089649 |
| dietary restriction and aging, 2009. | dietary restriction (dr) is a robust nongenetic, nonpharmacological intervention that is known to increase active and healthy lifespan in a variety of species. despite a variety of differences in the protocols and the way dr is carried out in different species, conserved relationships are emerging among multiple species. 2009 saw the field of dr mature with important mechanistic insights from multiple species. a report of lifespan extension in rapamycin-treated mice suggested that the tor pathwa ... | 2010 | 20096035 |
| srs2: the "odd-job man" in dna repair. | homologous recombination plays a key role in the maintenance of genome integrity, especially during dna replication and the repair of double-stranded dna breaks (dsbs). just a single un-repaired break can lead to aneuploidy, genetic aberrations or cell death. dsbs are caused by a vast number of both endogenous and exogenous agents including genotoxic chemicals or ionizing radiation, as well as through replication of a damaged template dna or the replication fork collapse. it is essential for cel ... | 2010 | 20096651 |
| role of yeast rad5 and its human orthologs, hltf and shprh in dna damage tolerance. | in the yeast saccharomyces cerevisiae, the rad6-rad18 dna damage tolerance pathway constitutes a major defense system against replication fork blocking dna lesions. the rad6-rad18 ubiquitin-conjugating/ligase complex governs error-free and error-prone translesion synthesis by specialized dna polymerases, as well as an error-free rad5-dependent postreplicative repair pathway. for facilitating replication through dna lesions, translesion synthesis polymerases copy directly from the damaged templat ... | 2010 | 20096653 |
| intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability. | various genes may influence intestinal barrier function, including magi2, myo9b, and pard3, which are associated with celiac disease. because direct measurement of intestinal permeability is difficult, antibodies against gliadin (aga) and baker's yeast (anti-saccharomyces cerevisiae antibodies [asca]) can be used as an indirect test. the objective of this study was to investigate whether intestinal permeability, represented by aga, was correlated with magi2, myo9b, and pard3. analyses were perfo ... | 2010 | 20096742 |
| imp dehydrogenase is recruited to the transcription complex through serine 2 phosphorylation of rna polymerase ii. | imp dehydrogenase (impdh) catalyzes the rate-limiting step in the de novo synthesis of guanine, namely the oxidation of imp to xmp with a concomitant reduction of nad+. in saccharomyces cerevisiae, a family of four closely-related genes, imd1, imd2 (also known as pur5), imd3, and imd4, encodes the putative impdh. although impdh synthesizes guanine in the cytoplasm, it has also been found in the nucleus, where it associates with nucleic acids in human cells. here, we further show that impdh is re ... | 2010 | 20097157 |
| the dna binding and 3'-end preferential activity of human tyrosyl-dna phosphodiesterase. | human tyrosyl-dna phosphodiesterase (tdp1) processes 3'-blocking lesions, predominantly 3'-phosphotyrosyl bonds resulting from the trapping of topoisomerase i (top1) cleavage complexes. the controversial ability of yeast tdp1 to hydrolyze 5'-phosphotyrosyl linkage between topoisomerase ii (top2) and dna raises the question whether human tdp1 possesses 5'-end processing activity. here we characterize the end-binding and cleavage preference of human tdp1 using single-stranded 5'- and 3'-fluorescei ... | 2010 | 20097655 |
| elevated levels of the polo kinase cdc5 override the mec1/atr checkpoint in budding yeast by acting at different steps of the signaling pathway. | checkpoints are surveillance mechanisms that constitute a barrier to oncogenesis by preserving genome integrity. loss of checkpoint function is an early event in tumorigenesis. polo kinases (plks) are fundamental regulators of cell cycle progression in all eukaryotes and are frequently overexpressed in tumors. through their polo box domain, plks target multiple substrates previously phosphorylated by cdks and mapks. in response to dna damage, plks are temporally inhibited in order to maintain th ... | 2010 | 20098491 |
| heterologous expression of human membrane receptors in the yeast saccharomyces cerevisiae. | due to their implication in numerous diseases like cancer, cystic fibrosis, epilepsy, hyperinsulinism, heart failure, hypertension, and alzheimer disease, membrane proteins (mps) represent around 50% of drug targets. however, only 204 crystal structures of mps have been solved. structural analysis requires large quantities of pure and active proteins. the majority of medically and pharmaceutically relevant mps are present in tissues at low concentration, which makes heterologous expression in la ... | 2010 | 20099141 |
| enhancement of cisplatin sensitivity by nsc109268 in budding yeast and human cancer cells is associated with inhibition of s-phase progression. | nsc109268 has been described previously as inhibitor of proteasomal degradation and of phosphatase 2calpha. in a yeast screen, we isolated nsc109268 as an agent altering sensitivity to dna-damaging agents. we found that nsc109268 and the related compound nsc109272 enhance cellular sensitivity to cis- and transplatin but reduce sensitivity to nitrogen mustard. we explored if similar effects could be found in human cancer cells and if cell cycle analysis could hint at the underlying molecular mech ... | 2010 | 20101404 |
| functional overlap between the structure-specific nucleases yen1 and mus81-mms4 for dna-damage repair in s. cerevisiae. | in eukaryotic cells, multiple dna repair mechanisms respond to a wide variety of dna lesions. homologous recombination-dependent repair provides a pathway for dealing with dna double-strand breaks and replication fork demise. a key step in this process is the resolution of recombination intermediates such as holliday junctions (hjs). recently, nucleases from yeast (yen1) and human cells (gen1) were identified that can resolve hj intermediates, in a manner analogous to the e. coli hj resolvase ru ... | 2010 | 20106725 |
| release of interleukins 6 and 8 induced by zymosan and mediated by map kinase and nf-kappab signaling pathways in human corneal fibroblasts. | zymosan is derived from the cell wall of yeast and induces immune responses associated with fungal infection. the effects of zymosan on the expression of proinflammatory cytokines, chemokines, and adhesion molecules and on the activity of signaling pathways were examined in cultured human corneal fibroblasts. | 2010 | 20107167 |
| nmr assignments of a stable processing intermediate of human frataxin. | frataxin, a nuclear encoded protein targeted to the mitochondrial matrix, has recently been implicated as an iron chaperone that delivers fe(ii) to the iron-sulfur assembly enzyme isu. during transport across the mitochondrial membrane, the n-terminal mitochondrial targeting sequence of frataxin is cleaved in a two-step process to produce the "mature" protein found within the matrix; however, n-terminally extended forms of the protein have also been observed in vivo as a result of processing def ... | 2010 | 20108066 |
| conservation of protein kinase a catalytic subunit sequences in the schistosome pathogens of humans. | camp-dependent protein kinases (pkas) are central mediators of camp signaling in eukaryotic cells. previously we identified a cdna which encodes for a pka catalytic subunit (pka-c) in schistosoma mansoni (smpka-c) that is required for adult schistosome viability in vitro. as such, smpka-c could potentially represent a novel schistosome chemotherapeutic target. here we sought to identify pka-c subunit orthologues in the other medically important schistosome species, schistosoma haematobium and sc ... | 2010 | 20109453 |
| interaction of saccharomyces boulardii with salmonella enterica serovar typhimurium protects mice and modifies t84 cell response to the infection. | salmonella pathogenesis engages host cells in two-way biochemical interactions: phagocytosis of bacteria by recruitment of cellular small gtp-binding proteins induced by the bacteria, and by triggering a pro-inflammatory response through activation of mapks and nuclear translocation of nf-kappab. worldwide interest in the use of functional foods containing probiotic bacteria for health promotion and disease prevention has increased significantly. saccharomyces boulardii is a non-pathogenic yeast ... | 2010 | 20111723 |
| rna turnover in human mitochondria: more questions than answers? | protein complexes responsible for rna degradation play important role in three key aspects of rna metabolism: they control stability of physiologically functional transcripts, remove the unnecessary rna processing intermediates and destroy aberrantly formed rnas. in mitochondria the post-transcriptional events seem to play a major role in regulation of gene expression, therefore rna turnover is of particular importance. despite many years of research, the details of this process are still a chal ... | 2010 | 20117077 |
| contamination with retinoic acid receptor agonists in two rivers in the kinki region of japan. | this study was conducted to investigate the agonistic activity against human retinoic acid receptor (rar) alpha in the lake biwa-yodo river and the ina river in the kinki region of japan. to accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of raralpha agonist contamination in the river basins. raralpha agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with ... | 2010 | 20117817 |
| the role of mrh domain-containing lectins in erad. | the endoplasmic reticulum (er) quality control system ensures that newly synthesized proteins in the early secretory pathway are in the correct conformation. polypeptides that have failed to fold into native conformers are subsequently retrotranslocated and degraded by the cytosolic ubiquitin-proteasome system, a process known as endoplasmic reticulum-associated degradation (erad). most of the polypeptides that enter the er are modified by the addition of n-linked oligosaccharides, and quality c ... | 2010 | 20118070 |
| sterol regulatory element binding proteins in fungi: hypoxic transcription factors linked to pathogenesis. | sterol regulatory element binding proteins (srebps) are membrane-bound transcription factors whose proteolytic activation is controlled by the cellular sterol concentration. mammalian srebps are activated in cholesterol-depleted cells and serve to regulate cellular lipid homeostasis. recent work demonstrates that srebp is functionally conserved in fungi. while the ability to respond to sterols is conserved, fungal srebps are hypoxic transcription factors required for adaptation to a low-oxygen e ... | 2010 | 20118213 |
| a conserved threonine residue in the juxtamembrane domain of the xa21 pattern recognition receptor is critical for kinase autophosphorylation and xa21-mediated immunity. | despite the key role that pattern recognition receptors (prrs) play in regulating immunity in plants and animals, the mechanism of activation of the associated non-arginine-aspartate (non-rd) kinases is unknown. the rice prr xa21 recognizes the pathogen-associated molecular pattern, ax21 (activator of xa21-mediated immunity). here we show that the xa21 juxtamembrane (jm) domain is required for kinase autophosphorylation. threonine 705 in the xa21 jm domain is essential for xa21 autophosphorylati ... | 2010 | 20118235 |
| wild-type and hupki (human p53 knock-in) murine embryonic fibroblasts: p53/arf pathway disruption in spontaneous escape from senescence. | research on cell senescence and immortalization of murine embryonic fibroblasts (mefs) has revealed important clues about genetic control of senescence in humans. to investigate senescence and genetic alterations in the p53 pathway that lead to senescence bypass in culture, we compared the behavior of mefs from wild-type mice with mefs from hupki mice, which harbor a humanized p53 gene. we found that humanizing the p53 gene in mice preserved major features of the mef senescence/immortalization p ... | 2010 | 20118236 |
| cleavage of zearalenone by trichosporon mycotoxinivorans to a novel nonestrogenic metabolite. | zearalenone (zon) is a potent estrogenic mycotoxin produced by several fusarium species most frequently on maize and therefore can be found in food and animal feed. since animal production performance is negatively affected by the presence of zon, its detoxification in contaminated plant material or by-products of bioethanol production would be advantageous. microbial biotransformation into nontoxic metabolites is one promising approach. in this study the main transformation product of zon forme ... | 2010 | 20118365 |
| crystal structures of saccharomyces cerevisiae tryptophanyl-trna synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design. | specific activation of amino acids by aminoacyl-trna synthetases is essential for maintaining translational fidelity. here, we present crystal structures of saccharomyces cerevisiae tryptophanyl-trna synthetase (strprs) in apo form and in complexes with various ligands. in each complex, there is a sulfate ion bound at the active site which mimics the alpha- or beta-phosphate group of atp during tryptophan activation. in particular, in one monomer of the strprs-trpnh(2)o complex, the sulfate ion ... | 2010 | 20123733 |
| structures of human mst3 kinase in complex with adenine, adp and mn2+. | the mst family is a subclass of mammalian serine/threonine kinases that are related to the yeast sterile-20 protein and are implicated in regulating cell growth and transformation. the mst3 protein contains a 300-residue catalytic domain and a 130-residue regulatory domain, which can be cleaved by caspase and activated by autophosphorylation, promoting apoptosis. here, five crystal structures of the catalytic domain of mst3 are presented, including a complex with adp and manganese, a unique cofa ... | 2010 | 20124694 |
| manganese-induced trafficking and turnover of the cis-golgi glycoprotein gpp130. | manganese is an essential element that is also neurotoxic at elevated exposure. however, mechanisms regulating mn homeostasis in mammalian cells are largely unknown. because increases in cytosolic mn induce rapid changes in the localization of proteins involved in regulating intracellular mn concentrations in yeast, we were intrigued to discover that low concentrations of extracellular mn induced rapid redistribution of the mammalian cis-golgi glycoprotein golgi phosphoprotein of 130 kda (gpp130 ... | 2010 | 20130081 |
| rvb1-rvb2: essential atp-dependent helicases for critical complexes. | rvb1 and rvb2 are highly conserved, essential aaa+ helicases found in a wide range of eukaryotes. the versatility of these helicases and their central role in the biology of the cell is evident from their involvement in a wide array of critical cellular complexes. rvb1 and rvb2 are components of the chromatin-remodeling complexes ino80, swr-c, and baf. they are also members of the histone acetyltransferase tip60 complex, and the recently identified r2tp complex present in saccharomyces cerevisia ... | 2010 | 20130677 |
| dnaa, orc, and cdc6: similarity beyond the domains of life and diversity. | to initiate chromosomal dna replication, specific proteins bind to the replication origin region and form multimeric and dynamic complexes. bacterial dnaa, the eukaryotic origin recognition complex (orc), and cdc6 proteins, most of which include an aaa+(-like) motif, play crucial roles in replication initiation. the importance of atp binding and hydrolysis in these proteins has recently become recognized. atp binding of escherichia coli dnaa is required for the formation of the activated form of ... | 2010 | 20130679 |
| mutation of his 834 in human anion exchanger 1 affects substrate binding. | anion exchanger 1 (ae1 or band 3) is responsible for cl(-)-hco3(-) exchange on erythrocyte membrane. previously, we showed that band 3 is fixed in an inward-facing conformation by specific modification of his 834 with depc, resulting in a strong inhibition of its anion transport activity. to clarify the physiological role of his 834, we evaluated the sulfate transport activities of various band 3 mutants: different mutants at his 834 and alanine mutants of peripheral residues around 834 (lys 829 ... | 2010 | 20132789 |
| challenges of steroid biotransformation with human cytochrome p450 monooxygenase cyp21 using resting cells of recombinant schizosaccharomyces pombe. | since cytochrome p450 monooxygenases enable the regio- and stereo-selective hydroxylation of c-h bonds, they are of outstanding interest for the synthesis of pharmaceuticals and fine chemicals. nevertheless, for industrial applications of such enzymes, e.g., steroid hydroxylation, several challenges like cofactor and oxygen supply, limited stability and activity, or low substrate solubility have to be overcome. to identify the limiting factors in a p450 catalyzed whole cell biotransformation, 21 ... | 2010 | 20132843 |
| functional residues on the surface of the n-terminal domain of yeast pms1. | saccharomyces cerevisiae mutlalpha is a heterodimer of mlh1 and pms1 that participates in dna mismatch repair (mmr). both proteins have weakly conserved c-terminal regions (ctds), with the ctd of pms1 harboring an essential endonuclease activity. these proteins also have conserved n-terminal domains (ntds) that bind and hydrolyze atp and bind to dna. to better understand pms1 functions and potential interactions with dna and/or other proteins, we solved the 2.5a crystal structure of yeast pms1 ( ... | 2010 | 20138591 |
| structural and functional characterization of recombinant human serum transferrin secreted from pichia pastoris. | serum transferrin is an iron-binding glycoprotein with a bilobal structure. it binds iron ions in the blood serum and delivers them into target cells via transferrin receptor. we identified structural and functional characteristics of recombinant human transferrin which is produced in the yeast pichia pastoris. using the signal sequence of the alpha factor of the yeast saccharomyces cerevisiae, high-level secretion was obtained, up to 30 mg/l of culture medium. correct processing at designed sit ... | 2010 | 20139607 |
| an extensive circuitry for cell wall regulation in candida albicans. | protein kinases play key roles in signaling and response to changes in the external environment. the ability of candida albicans to quickly sense and respond to changes in its environment is key to its survival in the human host. our guiding hypothesis was that creating and screening a set of protein kinase mutant strains would reveal signaling pathways that mediate stress response in c. albicans. a library of protein kinase mutant strains was created and screened for sensitivity to a variety of ... | 2010 | 20140194 |
| targeted metabolic labeling of yeast n-glycans with unnatural sugars. | metabolic labeling of glycans with synthetic sugar analogs has emerged as an attractive means for introducing nonnatural chemical functionality into glycoproteins. however, the complexities of glycan biosynthesis prevent the installation of nonnatural moieties at defined, predictable locations within glycoproteins at high levels of incorporation. here, we demonstrate that the conserved n-acetyglucosamine (glcnac) residues within chitobiose cores of n-glycans in the model organism saccharomyces c ... | 2010 | 20142501 |
| sars coronavirus protein 7a interacts with human ap4a-hydrolase. | the sars coronavirus (sars-cov) open reading frame 7a (orf 7a) encodes a 122 amino acid accessory protein. it has no significant sequence homology with any other known proteins. the 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. in this study we presen ... | 2010 | 20144233 |
| changes in the proteome of candida albicans in response to azole, polyene, and echinocandin antifungal agents. | the yeast candida albicans is an opportunistic human fungal pathogen and the cause of superficial and systemic infections in immunocompromised patients. the classes of antifungal agents most commonly used to treat candida infections are the azoles, polyenes, and echinocandins. in the present study, we identified changes in c. albicans protein abundance using two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectroscopy followi ... | 2010 | 20145080 |
| the role of paaac1 encoding a mitochondrial adp/atp carrier in the biosynthesis of extracellular glycolipids, mannosylerythritol lipids, in the basidiomycetous yeast pseudozyma antarctica. | pseudozyma antarctica produces large amounts of the glycolipid biosurfactants known as mannosylerythritol lipids (mel), which show not only excellent surface-active properties but also versatile biochemical actions. a gene homologous with a mitochondrial adp/atp carrier was dominantly expressed in p. antarctica under mel-producing conditions on the basis of previous gene expression analysis. the gene encoding the mitochondrial adp/atp carrier of p. antarctica (paaac1) contained a putative open r ... | 2010 | 20146402 |
| assigning roles to dna regulatory motifs using comparative genomics. | motivation: transcription factors (tfs) are crucial during the lifetime of the cell. their functional roles are defined by the genes they regulate. uncovering these roles not only sheds light on the tf at hand but puts it into the context of the complete regulatory network. results: here, we present an alignment- and threshold-free comparative genomics approach for assigning functional roles to dna regulatory motifs. we incorporate our approach into the gomo algorithm, a computational tool for d ... | 2010 | 20147307 |
| transgenic mice expressing mutant forms vcp/p97 recapitulate the full spectrum of ibmpfd including degeneration in muscle, brain and bone. | inclusion body myopathy associated with paget's disease of bone and frontotemporal dementia (ibmpfd) is a dominantly inherited degenerative disorder caused by mutations in the valosin-containing protein (vcp) gene. vcp (p97 in mouse, ter94 in drosophila melanogaster and cdc48 in saccharomyces cerevisiae) is a highly conserved aaa(+)-atpase that regulates a wide array of cellular processes. the mechanism of ibmpfd pathogenesis is unknown. towards elucidating the pathogenic mechanism we have devel ... | 2010 | 20147319 |
| atr contributes to telomere maintenance in human cells. | telomere maintenance is essential to preserve genomic stability and involves several telomere-specific proteins as well as dna replication and repair proteins. the kinase atr, which has a crucial function in maintaining genome integrity from yeast to human, has been shown to be involved in telomere maintenance in several eukaryotic organisms, including yeast, arabidopsis and drosophila. however, its role in telomere maintenance in mammals remains poorly explored. here, we report by using telomer ... | 2010 | 20147462 |
| detection of the atpase activity of the molecular chaperones hsp90 and hsp72 using the transcreenertm adp assay kit. | the molecular chaperone heat shock protein 90 (hsp90) is required for the correct folding and stability of a number of client proteins that are important for the growth and maintenance of cancer cells. heat shock protein 72 (hsp72), a co-chaperone of hsp90, is also emerging as an attractive cancer drug target. both proteins bind and hydrolyze adenosine triphosphate (atp), and atpase activity is essential for their function. inhibition of hsp90 atpase activity leads to the degradation of client p ... | 2010 | 20147598 |
| integrated single-cell analysis shows pichia pastoris secretes protein stochastically. | the production of heterologous proteins by secretion from cellular hosts is an important determinant for the cost of biotherapeutics. a single-cell analytical method called microengraving was used to examine the heterogeneity in secretion by the methylotrophic yeast pichia pastoris. we show that constitutive secretion of a human fc fragment by p. pastoris is not cell-cycle dependent, but rather fluctuates between states of high and low productivity in a stochastic manner. | 2010 | 20148400 |
| introducing antigen-binding sites in structural loops of immunoglobulin constant domains: fc fragments with engineered her2/neu-binding sites and antibody properties. | yeast surface display libraries of human igg1 fc regions were prepared in which loop sequences at the c-terminal tip of the ch3 domain were randomized. a high percentage of these library members bound to soluble cd64 and protein a indicating that the randomization step did not grossly interfere with the overall structure of the displayed fc. sorting these libraries by facs for binders against her2/neu yielded antigen-specific fc binders (fcab; fc antigen binding) of which one was affinity mature ... | 2010 | 20150180 |
| pseudomonas aeruginosa secreted factors impair biofilm development in candida albicans. | signal-mediated interactions between the human opportunistic pathogens pseudomonas aeruginosa and candida albicans affect virulence traits in both organisms. phenotypic studies revealed that bacterial supernatant from four p. aeruginosa strains strongly reduced the ability of c. albicans to form biofilms on silicone. this was largely a consequence of inhibition of biofilm maturation, a phenomenon also observed with supernatant prepared from non-clinical bacterial species. the effects of supernat ... | 2010 | 20150241 |
| production of heterologous proteins in plants: strategies for optimal expression. | plants are a promising expression system for the production of heterologous proteins, especially therapeutic proteins. currently the majority of therapeutic proteins are produced in mammalian cell lines or bacteria. in a few cases insects, yeast and fungi have been developed for production of human proteins. however, these expression systems have limitations in terms of suitability, cost, scalability, purification and post-translational modifications. therefore, alternative expression systems ar ... | 2010 | 20152894 |
| mechanisms of recombination between diverged sequences in wild-type and blm-deficient mouse and human cells. | double-strand breaks (dsbs) are particularly deleterious dna lesions for which cells have developed multiple mechanisms of repair. one major mechanism of dsb repair in mammalian cells is homologous recombination (hr), whereby a homologous donor sequence is used as a template for repair. for this reason, hr repair of dsbs is also being exploited for gene modification in possible therapeutic approaches. hr is sensitive to sequence divergence, such that the cell has developed ways to suppress recom ... | 2010 | 20154148 |
| detection of novel functional selectivity at m3 muscarinic acetylcholine receptors using a saccharomyces cerevisiae platform. | "functional selectivity", although new to many chemists and biologists only a few years ago, has now become a dominant theme in drug discovery. this concept posits that different ligands engender unique receptor conformations such that only a subset of signaling pathways linked to a given receptor are recruited. however, successful exploitation of the phenomenon to achieve pathway-based selectivity requires the ability to routinely detect it when assessing ligand behavior. we have utilized diffe ... | 2010 | 20155933 |
| hrmas 1h nmr conformational study of the resin-bound amyloid-forming peptide gnnqqny from the yeast prion sup35. | the conversion of soluble proteins to insoluble amyloid fibrils is associated with numerous human diseases. the peptide gnnqqny is a short segment of the yeast prion protein sup35 that previously has been found to form amyloid fibrils in a similar manner to the protein itself. the approach taken in this work was to attach this peptide sequence to an insoluble polymer matrix through solid phase peptide synthesis and give it the internal freedom to fold into its local conformation in an organic so ... | 2010 | 20155963 |
| affinity maturation of human botulinum neurotoxin antibodies by light chain shuffling via yeast mating. | botulism is caused by the botulinum neurotoxins (bonts), the most poisonous substance known. because of the high potency of bont, development of diagnostic and therapeutic antibodies for botulism requires antibodies of very high affinity. here we report the use of yeast mating to affinity mature bont antibodies by light chain shuffling. a library of immunoglobulin light chains was generated in a yeast vector where the light chain is secreted. the heavy chain variable region and the first domain ... | 2010 | 20156888 |
| wrn helicase defective in the premature aging disorder werner syndrome genetically interacts with topoisomerase 3 and restores the top3 slow growth phenotype of sgs1 top3. | werner syndrome (ws) is a premature aging disorder characterized by genomic instability. the wrn gene defective in ws encodes a protein with both helicase and exonuclease activities that interacts with proteins implicated in dna metabolism. to understand its genetic functions, we examined the ability of human wrn to rescue phenotypes associated with sgs1, the sole recq helicase in saccharomyces cerevisiae. wrn failed to rescue sgs1 sensitivity to the dna damaging agent methylmethane sulfonate or ... | 2009 | 20157511 |
| sirt6 stabilizes dna-dependent protein kinase at chromatin for dna double-strand break repair. | the sir2 chromatin regulatory factor links maintenance of genomic stability to life span extension in yeast. the mammalian sir2 family member sirt6 has been proposed to have analogous functions, because sirt6-deficiency leads to shortened life span and an aging-like degenerative phenotype in mice, and sirt6 knockout cells exhibit genomic instability and dna damage hypersensitivity. however, the molecular mechanisms underlying these defects are not fully understood. here, we show that sirt6 forms ... | 2009 | 20157594 |
| triclosan inhibition of mycobacterial inha in saccharomyces cerevisiae: yeast mitochondria as a novel platform for in vivo antimycolate assays. | to demonstrate the suitability of yeast to act as a novel biotechnological platform for conducting in vivo inhibition assays using drugs with low efficacies towards their mycobacterial targets, such as occurs in the situation with triclosan and inha. | 2010 | 20158608 |
| chemical inhibition of caax protease activity disrupts yeast ras localization. | proteins possessing a c-terminal caax motif, such as the ras gtpases, undergo extensive post-translational modification that includes attachment of an isoprenoid lipid, proteolytic processing and carboxylmethylation. inhibition of the enzymes involved in these processes is considered a cancer-therapeutic strategy. we previously identified nine in vitro inhibitors of the yeast caax protease rce1p in a chemical library screen (manandhar et al., 2007). here, we demonstrate that these agents disrupt ... | 2010 | 20162532 |
| active site remodelling accompanies thioester bond formation in the sumo e1. | e1 enzymes activate ubiquitin (ub) and ubiquitin-like (ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the e1 cys domain. the structural basis for these intermediates remains unknown. here we report crystal structures for human sumo e1 in complex with sumo adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 a, respectively. these structures show that side chain contacts to atp.mg are released after adenylat ... | 2010 | 20164921 |
| evolution and regulation of cellular periodic processes: a role for paralogues. | several cyclic processes take place within a single organism. for example, the cell cycle is coordinated with the 24 h diurnal rhythm in animals and plants, and with the 40 min ultradian rhythm in budding yeast. to examine the evolution of periodic gene expression during these processes, we performed the first systematic comparison in three organisms (homo sapiens, arabidopsis thaliana and saccharomyces cerevisiae) by using public microarray data. we observed that although diurnal-regulated and ... | 2010 | 20168326 |
| expression of functional mammal flavocytochrome b(558) in yeast: comparison with improved insect cell system. | activity of phagocyte nadph-oxidase relies on the assembly of five proteins, among them the transmembrane flavocytochrome b(558) (cytb(558)) which consists of a heterodimer of the gp91(phox) and p22(phox) subunits. the cytb(558) is the catalytic core of the nadph-oxidase that generates a superoxide anion from oxygen by using a reducing equivalent provided by nadph via fad and two hemes. we report a novel strategy to engineer and produce the stable and functional recombinant cytb(558) (rcytb(558) ... | 2010 | 20171157 |
| cloning the human vitamin d receptor into the ptwin-1 expression vector. | many of the actions of 1alpha,25-dihydroxyvitamin d3 [1,25(oh)2d3] are mediated by binding to the nuclear vitamin d receptor (vdr). vdr is a member of a superfamily of nuclear receptors that are ligand-dependent transcription factors. ligand binding induces conformational changes in the vdr that enable the receptor to interact with other coactivators to modulate gene transcription. in order to better characterize the binding of the vdr to 1,25(oh)2d3 and to analogs of 1,25(oh)2d3, we have cloned ... | 2010 | 20171280 |
| anaplasma phagocytophilum ats-1 is imported into host cell mitochondria and interferes with apoptosis induction. | anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, infects human neutrophils and inhibits mitochondria-mediated apoptosis. bacterial factors involved in this process are unknown. in the present study, we screened a genomic dna library of a. phagocytophilum for effectors of the type iv secretion system by a bacterial two-hybrid system, using a. phagocytophilum vird4 as bait. a hypothetical protein was identified as a putative effector, hereby named anaplasmatranslo ... | 2010 | 20174550 |
| function and metabolism of sirtuin metabolite o-acetyl-adp-ribose. | sirtuins catalyze the nad(+)-dependent deacetylation of target proteins, which are regulated by this reversible lysine modification. during deacetylation, the glycosidic bond of the nicotinamide ribose is cleaved to yield nicotinamide and the ribose accepts the acetyl group from substrate to produce o-acetyl-adp-ribose (oaadpr), which exists as an approximately 50:50 mixture of 2' and 3' isomers at neutral ph. discovery of this metabolite has fueled the idea that oaadpr may play an important rol ... | 2010 | 20176146 |
| the nizp1 krab and c2hr domains cross-talk for transcriptional regulation. | the nsd1 histone methyltransferase is involved in the outgrowth disorders sotos and weaver syndromes and childhood acute myeloid leukemia. nsd1 is a bona fida transcriptional co-repressor for nizp1 which is a protein including scan, krab, c2hr and zinc-finger domains. in this study the nizp1 krab-domain was identified to possess an intrinsic transcriptional activation capacity suppressed in cis by the presence of the c2hr domain. oppositely, the krab-domain supported c2hr domain mediated transcr ... | 2010 | 20176155 |
| replication fork arrest and rdna silencing are two independent and separable functions of the replication terminator protein fob1 of saccharomyces cerevisiae. | the replication terminator protein fob1 of saccharomyces cerevisiae is multifunctional, and it not only promotes polar replication fork arrest at the tandem ter sites located in the intergenic spacer region of rdna but also loads the nad-dependent histone deacetylase sir2 at ter sites via a protein complex called rent (regulator of nucleolar silencing and telophase exit). sir2 is a component of the rent complex, and its loading not only silences intrachromatid recombination in rdna but also rna ... | 2010 | 20179323 |
| immunogenic yeast-based fermentate for cold/flu-like symptoms in nonvaccinated individuals. | the common cold has a profound impact on employee attendance and productivity. seasonal influenza is responsible for approximately 200,000 hospitalizations and 36,000 deaths per year in the united states alone. over-the-counter medication efficacy has been questioned, and seasonal vaccination compliance issues abound. our previously reported randomized trial of an oral fermentation product found an adjuvant benefit for vaccinated individuals in terms of a significantly reduced incidence and dura ... | 2010 | 20180695 |
| taf1 differentially enhances androgen receptor transcriptional activity via its n-terminal kinase and ubiquitin-activating and -conjugating domains. | aberrant expression of androgen receptor (ar) coregulators has been linked to progression of prostate cancers to castration resistance. using the repressed transactivator yeast two-hybrid system, we found that tata binding protein-associated factor 1 (taf1) interacted with the ar. in tissue microarrays, taf1 was shown to steadily increase with duration of neoadjuvant androgen withdrawal and with progression to castration resistance. glutathione s-transferase pulldown assays established that taf1 ... | 2010 | 20181722 |
| tom1l is involved in a novel signaling pathway important for the il-2 production in jurkat t cells stimulated by cd3/cd28 co-ligation. | tom1l (target of myb-1 like) was identified as a binding partner for the full length and catalytically-active lck in a yeast 2-hybrid screening assay. here we show that in jurkat t cells stimulated by cd3/cd28 coligation where the expression of tom1l is reduced by lenti virus mediated-sirna results in a dramatically lower il-2 production. the production of il-2 in sirna treated cells stimulated with pma/ionomycin was not affected indicating an involvement of tom1l in a pathway proximal of tcr an ... | 2010 | 20182632 |
| inferring genetic interactions via a nonlinear model and an optimization algorithm. | biochemical pathways are gradually becoming recognized as central to complex human diseases and recently genetic/transcriptional interactions have been shown to be able to predict partial pathways. with the abundant information made available by microarray gene expression data (mged), nonlinear modeling of these interactions is now feasible. two of the latest advances in nonlinear modeling used sigmoid models to depict transcriptional interaction of a transcription factor (tf) for a target gene, ... | 2010 | 20184777 |
| assembly and oligomerization of human atp synthase lacking mitochondrial subunits a and a6l. | here we study atp synthase from human rho0 (rho zero) cells by clear native electrophoresis (cne or cn-page) and show that atp synthase is almost fully assembled in spite of the absence of subunits a and a6l. this identifies subunits a and a6l as two of the last subunits to complete the atp synthase assembly. minor amounts of dimeric and even tetrameric forms of the large assembly intermediate were preserved under the conditions of cne, suggesting that it associated further into higher order str ... | 2010 | 20188060 |
| a trk/hkt-type k+ transporter from trypanosoma brucei. | the molecular mechanisms of k(+) homeostasis are only poorly understood for protozoan parasites. trypanosoma brucei subsp. parasites, the causative agents of human sleeping sickness and nagana, are strictly extracellular and need to actively concentrate k(+) from their hosts' body fluids. the t. brucei genome contains two putative k(+) channel genes, yet the trypanosomes are insensitive to k(+) antagonists and k(+) channel-blocking agents, and they do not spontaneously depolarize in response to ... | 2010 | 20190075 |
| predicting highly-connected hubs in protein interaction networks by qsar and biological data descriptors. | hub proteins (those engaged in most physical interactions in a protein interaction network (pin) have recently gained much research interest due to their essential role in mediating cellular processes and their potential therapeutic value. it is straightforward to identify hubs if the underlying pin is experimentally determined; however, theoretical hub prediction remains a very challenging task, as physicochemical properties that differentiate hubs from less connected proteins remain mostly unc ... | 2009 | 20198194 |
| linking h3k79 trimethylation to wnt signaling through a novel dot1-containing complex (dotcom). | epigenetic modifications of chromatin play an important role in the regulation of gene expression. kmt4/dot1 is a conserved histone methyltransferase capable of methylating chromatin on lys79 of histone h3 (h3k79). here we report the identification of a multisubunit dot1 complex (dotcom), which includes several of the mixed lineage leukemia (mll) partners in leukemia such as enl, af9/mllt3, af17/mllt6, and af10/mllt10, as well as the known wnt pathway modifiers trrap, skp1, and beta-catenin. we ... | 2010 | 20203130 |
| extensive proteomic screening identifies the obesity-related nyggf4 protein as a novel lrp1-interactor, showing reduced expression in early alzheimer's disease. | abstract: | 2010 | 20205790 |
| rab4 interacts with the human p-glycoprotein and modulates its surface expression in multidrug resistant k562 cells. | p-glycoprotein (p-gp) is a plasma membrane glycoprotein that has been signaled as a primary cause of multidrug resistance (mdr) in tumors. we performed a yeast 2-hybrid screen using the c-terminal domain of p-gp and identified 2 small gtpases involved in vesicular trafficking, rab4 and rab14, which complex with p-gp. the overexpression of gfp-rab4, either transiently or stably, but not of rab14, in k562adr cells decreased the presence of p-gp in the cell surface. as a result, expression of this ... | 2011 | 20209493 |
| interaction of testisin with maspin and its impact on invasion and cell death resistance of cervical cancer cells. | previous studies have shown that testisin promotes malignant transformation in cancer cells. to define the mechanism of testisin-induced carcinogenesis, we performed yeast two-hybrid analysis and identified maspin, a tumor suppressor protein, as a testisin-interacting molecule. the direct interaction and cytoplasmic co-localization of testisin with maspin was confirmed by immunoprecipitation and confocal analysis, respectively. in cervical cancer cells, maspin modulated cell death and invasion; ... | 2010 | 20211623 |
| brd7, a subunit of swi/snf complexes, binds directly to brca1 and regulates brca1-dependent transcription. | we carried out a yeast two-hybrid screen using a brca1 bait composed of amino acids 1 to 1142 and identified brd7 as a novel binding partner of brca1. this interaction was confirmed by coimmunoprecipitation of endogenous brca1 and brd7 in t47d and hek-293 cells. brd7 is a bromodomain containing protein, which is a subunit of pbaf-specific swi/snf chromatin remodeling complexes. to determine the functional consequences of the brca1-brd7 interaction, we investigated the role of brd7 in brca1-depen ... | 2010 | 20215511 |
| the conserved mitochondrial twin cx9c protein cmc2 is a cmc1 homologue essential for cytochrome c oxidase biogenesis. | mitochondrial copper metabolism and delivery to cytochrome c oxidase and mitochondrially localized cuzn-superoxide dismutase (sod1) requires a growing number of intermembrane space proteins containing a twin cx(9)c motif. among them, cmc1 was recently identified by our group. here we describe another conserved mitochondrial metallochaperone-like protein, cmc2, a close homologue of cmc1, whose function affects both cytochrome c oxidase and sod1. in the yeast saccharomyces cerevisiae, cmc2 localiz ... | 2010 | 20220131 |
| mitotic catastrophe induced by overexpression of budding yeast rad2p. | mitotic catastrophe provokes endopolyploidy, giant cell formation and, eventually, delayed cell death. mitotic catastrophe is induced by defective cell cycle checkpoints and by some anticancer drugs, ionizing radiation and microtubule-destabilizing agents. rad2 is a yeast homologue of xpg, which is a human endonuclease involved in nucleotide excision repair. here we show that rad2p overexpression alone, in the absence of extrinsic dna damage, causes cell growth arrest and mitotic catastrophe. in ... | 2010 | 20222011 |
| tryptophan scanning analysis of the membrane domain of ctr-copper transporters. | membrane proteins of the ctr family mediate cellular copper uptake in all eukaryotic cells and have been shown to participate in uptake of platinum-based anticancer drugs. despite their importance for life and the clinical treatment of malignancies, directed biochemical studies of ctr proteins have been difficult because high-resolution structural information is missing. building on our recent 7a structure of the human copper transporter hctr1, we present the results of an extensive tryptophan-s ... | 2010 | 20224886 |
| the role of mitochondrial network dynamics in the pathogenesis of charcot-marie-tooth disease. | mitochondrial dysfunction plays a relevant role in the pathogenesis of neurological and neuromuscular diseases. mitochondria may be involved as a primary defect of either the mtdna or nuclear genome encoded subunits of the respiratory chain. these organelles have also been directly involved in the pathogenesis of mendelian neurodegenerative disorders caused by mutations in nuclear-encoded proteins targeted to mitochondria, such as friedreich ataxia, hereditary spastic paraplegia, or some monogen ... | 2009 | 20225023 |