Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| identification and functional characterization of the 2-hydroxy fatty n-acyl-delta3(e)-desaturase from fusarium graminearum. | delta3(e)-unsaturated fatty acids are characteristic components of glycosylceramides from some fungi, including also human- and plant-pathogenic species. the function and genetic basis for this unsaturation is unknown. for fusarium graminearum, which is pathogenic to grasses and cereals, we could show that the level of delta3-unsaturation of glucosylceramide (glccer) was highest at low temperatures and decreased when the fungus was grown above 28 degrees c. with a bioinformatics approach, we ide ... | 2008 | 18981185 |
| mis-targeted methylation in rrna can severely impair ribosome synthesis and activity. | eukaryotic rrnas contain scores of two major types of nucleotide modifications, 2'-o-methylation (nm) and pseudouridylation (psi). both types are known to alter the stability and dynamics of rna folding. in eukaryotes, these modifications are created by small nucleolar rnps (snornps) with site-specificity provided by the snorna component. little is yet known about the influence of such modifications on ribosome synthesis or activity, although in a few cases depletions of natural modifications ha ... | 2008 | 18981724 |
| differential activities of cellular and viral macro domain proteins in binding of adp-ribose metabolites. | macro domain is a highly conserved protein domain found in both eukaryotes and prokaryotes. macro domains are also encoded by a set of positive-strand rna viruses that replicate in the cytoplasm of animal cells, including coronaviruses and alphaviruses. the functions of the macro domain are poorly understood, but it has been suggested to be an adp-ribose-binding module. we have here characterized three novel human macro domain proteins that were found to reside either in the cytoplasm and nucleu ... | 2009 | 18983849 |
| excision of the oxidatively formed 5-hydroxyhydantoin and 5-hydroxy-5-methylhydantoin pyrimidine lesions by escherichia coli and saccharomyces cerevisiae dna n-glycosylases. | (5r) and (5s) diastereomers of 1-[2-deoxy-beta-d-erythro-pentofuranosyl]-5-hydroxyhydantoin (5-oh-dhyd) and 1-[2-deoxy-beta-d-erythro-pentofuranosyl]-5-hydroxy-5-methylhydantoin (5-oh-5-me-dhyd) are major oxidation products of 2'-deoxycytidine and thymidine respectively. if not repaired, when present in cellular dna, these base lesions may be processed by dna polymerases that induce mutagenic and cell lethality processes. | 2009 | 18983898 |
| ynk1, the yeast homolog of human metastasis suppressor nm23, is required for repair of uv radiation- and etoposide-induced dna damage. | in humans, nm23-h1 is a metastasis suppressor whose expression is reduced in metastatic melanoma and breast carcinoma cells, and which possesses the ability to inhibit metastatic growth without significant impact on the transformed phenotype. nm23-h1 exhibits three enzymatic activities in vitro, each with potential to maintain genomic stability, a 3'-5' exonuclease and two kinases, nucleoside diphosphate kinase (ndpk), and protein histidine kinase. herein we have investigated the potential contr ... | 2009 | 18983998 |
| hepatitis c virus infection protein network. | a proteome-wide mapping of interactions between hepatitis c virus (hcv) and human proteins was performed to provide a comprehensive view of the cellular infection. a total of 314 protein-protein interactions between hcv and human proteins was identified by yeast two-hybrid and 170 by literature mining. integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with hcv are enriched in highly central and interconnected proteins. a global analysis ... | 2008 | 18985028 |
| phosphorylation of cardiac troponin i by mammalian sterile 20-like kinase 1. | mst1 (mammalian sterile 20-like kinase 1) is a ubiquitously expressed serine/threonine kinase and its activation in the heart causes cardiomyocyte apoptosis and dilated cardiomyopathy. its myocardial substrates, however, remain unknown. in a yeast two-hybrid screen of a human heart cdna library with a dominant-negative mst1 (k59r) mutant used as bait, ctn [cardiac tn (troponin)] i was identified as an mst1-interacting protein. the interaction of ctni with mst1 was confirmed by co-immunoprecipita ... | 2009 | 18986304 |
| gene expression data analysis using a novel approach to biclustering combining discrete and continuous data. | many different methods exist for pattern detection in gene expression data. in contrast to classical methods, biclustering has the ability to cluster a group of genes together with a group of conditions (replicates, set of patients or drug compounds). however, since the problem is np-complex, most algorithms use heuristic search functions and therefore might converge towards local maxima. by using the results of biclustering on discrete data as a starting point for a local search function on con ... | 2008 | 18989045 |
| 80k-h interacts with inositol 1,4,5-trisphosphate (ip3) receptors and regulates ip3-induced calcium release activity. | inositol 1,4,5-trisphosphate receptors (ip3rs) are intracellular channel proteins that mediate calcium (ca2+) release from the endoplasmic reticulum, and they are involved in many biological processes (e.g. fertilization, secretion, and synaptic plasticity). recent reports show that ip3r activity is strictly regulated by several interacting molecules (e.g. ip3r binding protein released with inositol 1,4,5-trisphosphate, huntingtin, presenilin, danger, and cytochrome c), and perturbation of this ... | 2009 | 18990696 |
| structure and function of the human na+/h+ exchanger isoform 1. | sodium proton exchangers (nhes) constitute a large family of polytopic membrane protein transporters found in organisms across all domains of life. they are responsible for the exchange of protons for sodium ions. in archaea, bacteria, yeast and plants they provide increased salt tolerance by removing sodium in exchanger for extracellular protons. in humans they have a host of physiological functions, the most prominent of which is removal of intracellular protons in exchange for extracellular s ... | 2008 | 19001864 |
| human beta-defensin-2 induction in human foreskin keratinocyte by synergetic stimulation with foods and escherichia coli. | we established a real-time quantitative rt-pcr assay that permits rapid and sensitive screening of foods that increase the human beta-defensin-2 (hbd-2) mrna level in human foreskin keratinocyte (hfk) cells. the range of hbd-2 mrna concentrations suitable for the assay was between 8 x 10(-11) m (39-cycle amplification) and 8 x 10(-18) m (13-cycle amplification) as calibrated with standard hbd-2 cdna. with this assay system, it was found that the stimulation of hfk cells by the addition of yeast ... | 2003 | 19003218 |
| mdr quinone oxidoreductases: the human and yeast zeta-crystallins. | the medium-chain dehydrogenase/reductase (mdr) superfamily can be divided into zn-containing and zn-lacking proteins. zn-containing mdrs are generally well-known enzymes, mostly acting as dehydrogenases. the non-zn mdr are much less studied, and classified in several families of nadp(h)-dependent reductases, including quinone oxidoreductases (qor). zeta-crystallins are the best studied group of qor, have a structural function in the lens of several mammals, exhibit ortho-quinone reductase activi ... | 2009 | 19007762 |
| sumoylation and de-sumoylation: wrestling with life's processes. | the small ubiquitin-like modifier (sumo) is a ubiquitin-like protein that covalently modifies a large number of cellular proteins. sumo modification has emerged as an important regulatory mechanism for protein function and localization. sumoylation is a dynamic process that is mediated by activating (e1), conjugating (e2), and ligating (e3) enzymes and readily reversed by a family of ubiquitin-like protein-specific proteases (ulp) in yeast and sentrin/sumo-specific proteases (senp) in human. thi ... | 2009 | 19008217 |
| alternative splicing in class v myosins determines association with rab10. | rab proteins influence vesicle trafficking pathways through the assembly of regulatory protein complexes. previous investigations have documented that rab11a and rab8a can interact with the tail region of myosin vb and regulate distinct trafficking pathways. we have now determined that a related rab protein, rab10, can interact with myosin va, myosin vb, and myosin vc. rab10 localized to a system of tubules and vesicles that have partially overlapping localization with rab8a. both rab8a and rab1 ... | 2009 | 19008234 |
| receptor for activated c-kinase 1, a novel binding partner of adiponectin receptor 1. | adiponectin is an adipose tissue derived hormone with anti-diabetic and insulin-sensitizing properties. two adiponectin receptors, adipor1 and adipor2, have recently been identified, yet the signaling pathways triggered through adiponectin receptors remain to be elucidated. using a yeast two-hybrid screen, we identified an adaptor protein, receptor for activated protein kinase c1 (rack1), as an interacting partner of human adipor1. rack1 was confirmed to interact with adipor1 by co-immunoprecipi ... | 2009 | 19010305 |
| sirt1 regulates the ribosomal dna locus: epigenetic candles twinkle longevity in the christmas tree. | ribosomal rna (rrna) genes arrange themselves in a tandem pattern in nucleolus and during the transcription of rrna genes, the elongating nascent rrna transcripts create a structure called christmas tree. rrna genes in the rdna locus can be either active or silent depending on the epigenetic regulation of the chromatin structure. yeast sir2 (silent information regulator 2) protein containing complexes can repress the recombination in the rdna locus and subsequently extend the replicative lifespa ... | 2009 | 19010308 |
| a disulfide-bond a oxidoreductase-like protein (dsba-l) regulates adiponectin multimerization. | impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. we have identified an adiponectin-interacting protein, previously named gst-kappa, by yeast 2-hybrid screening. the adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other gst isoforms. however, this protein shares high sequence and secondary structure homolo ... | 2008 | 19011089 |
| phosphorylation of the par-1 polarity kinase by protein kinase d regulates 14-3-3 binding and membrane association. | the par-1 protein kinases are conserved from yeast to humans, where they function as key polarity determinants. the mammalian par-1 family is comprised of 4 members (par-1a, -b, -c, and -d). previously, we demonstrated that atypical protein kinase c (apkc) phosphorylates the par-1 kinases on a conserved threonine residue (t595) to regulate localization and kinase activity. here, we demonstrate that par-1b is also regulated by another arm of the pkc pathway, one that involves novel pkcs (npkc) an ... | 2008 | 19011111 |
| cold induced botrytis cinerea enolase (bcenol-1) functions as a transcriptional regulator and is controlled by camp. | botrytis cinerea is a necrotrophic fungal plant pathogen that can survive, grow and infect crops under cold stress. in an attempt to understand the molecular mechanisms leading to cold tolerance of this phytopathogen, we identified an enolase, bcenol-1. bcenol-1 encodes a 48 kda protein that shows high identity to yeast, arabidopsis and human enolases (72, 63 and 63%, respectively). northern analysis confirms that an increase in transcript abundance of bcenol-1 was observed when b. cinerea mycel ... | 2009 | 19011901 |
| dbf4-dependent cdc7 kinase links dna replication to the segregation of homologous chromosomes in meiosis i. | meiosis differs from mitosis in that dna replication is followed by the segregation of homologous chromosomes but not sister chromatids. this depends on the formation of interhomolog connections through crossover recombination and on the attachment of sister kinetochores to microtubules emanating from the same spindle pole. we show that in yeast, the dbf4-dependent cdc7 kinase (ddk) provides a link between premeiotic s phase, recombination, and monopolar attachment. independently from its establ ... | 2008 | 19013276 |
| contribution of the c-terminal region within the catalytic core domain of hiv-1 integrase to yeast lethality, chromatin binding and viral replication. | hiv-1 integrase (in) is a key viral enzymatic molecule required for the integration of the viral cdna into the genome. additionally, hiv-1 in has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. interestingly, previous studies have demonstrated that the expression of hiv-1 in induces the lethal phenotype in some strains of saccharomyces cerevisiae. in this study, we performed mutagenic ... | 2008 | 19014595 |
| cloning and expression of a new recombinant thrombolytic and anthithrombotic agent - a staphylokinase variant. | to develop a more potent antithrombin agent with thrombolytic and antiplatelet properties, a new staphylokinase (sak) variant was constructed. the kringle 2 domain (k2) of tissue type-plasminogen activator (t-pa) containing a fibrin-specific binding site (i), the rgd sequence (arg-gly-asp) for the prevention of platelet aggregation (ii) and the antithrombotic agent - hirulog (iii) was assembled to the c-terminal part of recombinant staphylokinase (r-sak). cdna for the hybrid protein sak-rgd-k2-h ... | 2009 | 19018330 |
| scythe/bat3 regulates apoptotic cell death induced by papillomavirus binding factor in human osteosarcoma. | papillomavirus binding factor (pbf) was first identified as a transcription factor regulating the promoter activity of human papillomavirus. we previously demonstrated that pbf is an osteosarcoma-associated antigen and 92% of osteosarcoma tissues express pbf in the nucleus. moreover, pbf-positive osteosarcoma has a significantly poorer prognosis than that with negative expression of pbf. in the present study, we assessed the biological role of pbf in cell survival. overexpression of pbf induced ... | 2009 | 19018758 |
| malassezia furfur fingerprints as possible markers for human phylogeography. | malassezia furfur was the first species described within the cosmopolitan yeast genus malassezia, which now comprises 13 species. reported isolation rates of these species from healthy and diseased human skin show geographic variations. pcr-fingerprinting with the wild-type phage m13 primer (5'-gagggtggcggttct-3') was applied to investigate phylogeographic associations of m. furfur strains isolated from scandinavians residing permanently in greece, in comparison to clinical isolates from greek, ... | 2009 | 19020555 |
| identification of holliday junction resolvases from humans and yeast. | four-way dna intermediates, also known as holliday junctions, are formed during homologous recombination and dna repair, and their resolution is necessary for proper chromosome segregation. here we identify nucleases from saccharomyces cerevisiae and human cells that promote holliday junction resolution, in a manner analogous to that shown by the escherichia coli holliday junction resolvase ruvc. the human holliday junction resolvase, gen1, and its yeast orthologue, yen1, were independently iden ... | 2008 | 19020614 |
| aggresome-forming ttrap mediates pro-apoptotic properties of parkinson's disease-associated dj-1 missense mutations. | mutations in park7 dj-1 have been associated with autosomal-recessive early-onset parkinson's disease (pd). this gene encodes for an atypical peroxiredoxin-like peroxidase that may act as a regulator of transcription and a redox-dependent chaperone. although large gene deletions have been associated with a loss-of-function phenotype, the pathogenic mechanism of several missense mutations is less clear. by performing a yeast two-hybrid screening from a human fetal brain library, we identified tra ... | 2009 | 19023331 |
| the fox1 ferroxidase of chlamydomonas reinhardtii: a new multicopper oxidase structural paradigm. | multicopper oxidases (mco) contain at least four copper atoms arrayed in three distinct ligand fields supported by two canonical structural features: (1) multiples of the cupredoxin fold and (2) four unique sequence elements that include the ten histidine and one cysteine ligands to the four copper atoms. ferroxidases are a subfamily of mco proteins that contain residues supporting a specific reactivity towards ferrous iron; these mcos play a vital role in iron metabolism in bacteria, algae, fun ... | 2009 | 19023602 |
| genetic polymorphism in long-lived people: cues for the presence of an insulin/igf-pathway-dependent network affecting human longevity. | longevity in yeast, nematodes, fruit flies and mice is affected by mutations in the insulin/igf-1 or homologous pathways. studies on long-living people revealed some associations between genetic variants of the insulin/igf-1 pathway and longevity. here, we review such investigations, and we will report human longevity association studies regarding the variability of genes which modulate lifespan in model organisms by interacting with the insulin/igf-1 pathway. these studies will be presented in ... | 2009 | 19027825 |
| the hect domain of trip12 ubiquitinates substrates of the ubiquitin fusion degradation pathway. | the ubiquitin fusion degradation (ufd) pathway is a proteolytic system conserved in yeast and mammals in which an uncleavable ubiquitin moiety linked to the n terminus of a protein functions as a degradation signal of the fusion protein. although key components of the ufd pathway in yeast have been identified, the e3 enzyme of the human ufd pathway has not been studied. in this work, we show that trip12 is the e3 enzyme of the human ufd pathway. thus, trip12 catalyzes in vitro ubiquitination of ... | 2009 | 19028681 |
| functionality and substrate specificity of human box h/aca guide rnas. | a large number of box h/aca rnas have been identified in human cells, and have been predicted to account for nearly all pseudouridylation sites in human rrnas. however, the function of these mammalian h/aca rnas in directing pseudouridylation has been verified experimentally in only two cases. in this study, we used three in vitro reconstitution systems, including yeast and mammalian systems, to test the function of seven h/aca rnas guiding16 pseudouridylation sites. our results verified 12 of t ... | 2009 | 19033376 |
| [study on the relationship between human cytidine deaminase gene polymorphisms and ara-c sensitivity]. | to study the relationship between coding single-nucleotide polymorphisms (csnps) in the human cytidine deaminase (cda) gene and cytosine arabinoside (ara-c) sensitivity in childhood acute leukemia (al). | 2008 | 19035178 |
| identification of protamine 1 as a novel cancer-testis antigen in early chronic lymphocytic leukaemia. | early chronic lymphocytic leukaemia (cll) is an ideal disease for immunotherapy. we previously showed that semg 1 is a cancer-testis (ct) antigen in cll. in this study, semg 1 was applied as the bait in a yeast two-hybrid system of a testicular cdna library. seven clones were isolated and protamine (prm) 1 was identified as a novel ct antigen in early cll. prm1 transcripts were detected in 11/41 (26.8%) patients. prm 1 protein was also expressed but heterogeneously within individual patients. of ... | 2009 | 19036087 |
| knockdown of p180 eliminates the terminal differentiation of a secretory cell line. | we have previously reported that the expression in yeast of an integral membrane protein (p180) of the endoplasmic reticulum (er), isolated for its ability to mediate ribosome binding, is capable of inducing new membrane biogenesis and an increase in secretory capacity. to demonstrate that p180 is necessary and sufficient for terminal differentiation and acquisition of a secretory phenotype in mammalian cells, we studied the differentiation of a secretory cell line where p180 levels had been sig ... | 2009 | 19037105 |
| vac14 nucleates a protein complex essential for the acute interconversion of pi3p and pi(3,5)p(2) in yeast and mouse. | the signalling lipid pi(3,5)p(2) is generated on endosomes and regulates retrograde traffic to the trans-golgi network. physiological signals regulate rapid, transient changes in pi(3,5)p(2) levels. mutations that lower pi(3,5)p(2) cause neurodegeneration in human patients and mice. the function of vac14 in the regulation of pi(3,5)p(2) was uncharacterized previously. here, we predict that yeast and mammalian vac14 are composed entirely of heat repeats and demonstrate that vac14 exerts an effect ... | 2008 | 19037259 |
| impaired dendritic cell maturation and cytokine production in patients with chronic mucocutanous candidiasis with or without apeced. | patients with chronic mucocutaneous candidiasis (cmc) suffer persistent infections with the yeast candida. cmc includes patients with autoimmune regulator (aire) gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (apeced), and patients without known mutations. cmc patients have dysregulated cytokine production, and dendritic cells (dcs), as central orchestrators, may underlie pathogenic disease mechanisms. in 29 patients with cmc (13 with apeced) and controls, ... | 2008 | 19037923 |
| characteristics of fc-independent human antimannan antibody-mediated alternative pathway initiation of c3 deposition to candida albicans. | the complement system has an important role in host resistance to systemic candidiasis but regulation of complement activation by candida albicans remains poorly defined. previous studies have identified a requirement for naturally occurring antimannan igg antibody in initiation of c3 opsonization of c. albicans through either the classical or alternative pathway. this study characterized antibody-dependent initiation of the alternative pathway using the recombinant human monoclonal antimannan f ... | 2009 | 19038459 |
| chemical synthesis of oligodeoxyribonucleotides containing n3- and o4-carboxymethylthymidine and their formation in dna. | humans are exposed to n-nitroso compounds from both endogenous and exogenous sources. many n-nitroso compounds can be metabolically activated to give diazoacetate, which can result in the carboxymethylation of dna. the remarkable similarity in p53 mutations found in human gastrointestinal tumors and in shuttle vector studies, where the human p53 gene-containing vector was treated with diazoacetate and propagated in yeast cells, suggests that diazoacetate might be an important etiological agent f ... | 2009 | 19042973 |
| protein phosphatase dusp26 associates with kif3 motor and promotes n-cadherin-mediated cell-cell adhesion. | recent studies have demonstrated essential functions for kif3, a microtubule-directed protein motor, in subcellular transport of several cancer-related proteins, including the beta-catenin-cadherin(s) complex. in this study, we report identification of the protein-phosphatase dusp26 as a novel regulator of the kif3 motor. here we undertake yeast two-hybrid screening and identify kif3a, a motor subunit of the kif3 heterotrimeric complex, as a novel dusp26-binding protein. co-immunoprecipitation a ... | 2009 | 19043453 |
| recruitment of rna polymerase ii cofactor pc4 to dna damage sites. | the multifunctional nuclear protein positive cofactor 4 (pc4) is involved in various cellular processes including transcription, replication, and chromatin organization. recently, pc4 has been identified as a suppressor of oxidative mutagenesis in escherichia coli and saccharomyces cerevisiae. to investigate a potential role of pc4 in mammalian dna repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. we found a clear ac ... | 2008 | 19047459 |
| mrna nuclear export and human disease. | export of mrna from the nucleus is a central process in eukaryotic gene expression that has been implicated in several human diseases. much of our understanding of how an mrna is transported to the cytoplasm is derived from studies using yeast and fly models. we present here different mechanisms by which aberrant nuclear retention of mrna can cause human disease. emerging evidence that implicates the mrna export factor gle1 in two lethal motor neuron disorders is discussed and we highlight surpr ... | 2008 | 19048072 |
| pbt, a novel vector for tetracycline-regulated yeast three-hybrid assay. | a novel yeast three-hybrid (y3h) vector pbt was developed, which contains a tetracycline (tet)-sensitive transactivator (tta) expression unit and a tet-responsive element (tre)-driven 3rd protein expression unit within a single plasmid. to optimize tta expression levels, several promoters for driving tta expression were tested, and the weakest human cytomegalovirus (cmv) promoter showed the best induction/background ratio. culturing yeast cells in different doses of doxycycline (dox) resulted in ... | 2009 | 19050013 |
| chinese red yeast rice versus lovastatin effects on prostate cancer cells with and without androgen receptor overexpression. | chinese red yeast rice (ryr), a food herb made by fermenting monascus purpureus went yeast on white rice, contains a mixture of eight different monacolins that inhibit cholesterogenesis and also red pigments with antioxidant properties. monacolin k (mk) is identical to lovastatin (lv). both lv and ryr contain statins, which could inhibit de novo cholesterogenesis, which is critical to the growth of tumor cells. dysregulation of the cholesterol biosynthetic pathway has been demonstrated during pr ... | 2008 | 19053857 |
| the tp53inp2 protein is required for autophagy in mammalian cells. | using a bioinformatic approach, we identified a tp53inp1-related gene encoding a protein with 30% identity with tumor protein 53-induced nuclear protein 1 (tp53inp1), which was named tp53inp2. tp53inp1 and tp53inp2 sequences were found in several species ranging from homo sapiens to drosophila melanogaster, but orthologues were found neither in earlier eukaryotes nor in prokaryotes. to gain insight into the function of the tp53inp2 protein, we carried out a yeast two-hybrid screening that showed ... | 2009 | 19056683 |
| functional characterization of three cyp21a2 sequence variants (p.a265v, p.w302s, p.d322g) employing a yeast co-expression system. | congenital adrenal hyperplasia (cah) due to steroid 21-hydroxylase (cyp21a2) deficiency is the commonest inborn error in steroid hormone biosynthesis. functional in vitro assessment of mutant activity generally correlates well with clinical phenotype and therefore has contributed greatly to phenotype prediction in this cah variant. three cyp21a2 sequence variants (g.1641c>t, p.a265v; g.1752g>c, p.w302s; and g.2012a>g, p.d322g) identified in patients with non-classic and simple virilizing cah wer ... | 2009 | 19058224 |
| activation of hiv-1 gag-specific cd8+ t cells by yeast-derived vlp-pulsed dendritic cells is influenced by the level of mannose on the vlp antigen. | dendritic cells (dcs) are professional antigen-presenting cells that possess a unique capacity to cross-present exogenous antigens efficiently to cd8(+) t cells. we previously demonstrated that monocyte-derived dcs (mddcs) pulsed with yeast-derived hiv-1 gag virus-like particles (vlps) were able to activate gag-specific cd8(+) t cells from hiv-1-infected individuals. yeast vlps are abundantly mannosylated (high-mannose type: hmvlps) and are highly immunogenic. because lectin receptors are shown ... | 2009 | 19059495 |
| organization of human replicon: singles or zipping couples? | according to a general paradigm, proper dna duplication from each replication origin is ensured by two protein complexes termed replisomes. in prokaryotes and in budding yeast saccharomyces cerevisiae, these two replisomes seem to be associated with one another until dna replication initiated from the origin has finished. this arrangement results in the formation of the loop of newly synthesized dna. however, arrangement of replisomes in other eukaryotic organisms including vertebrate cells is l ... | 2009 | 19063972 |
| chromatin reassembly signals the end of dna repair. | the packaging of the eukaryotic genome into chromatin provides a formidable obstacle to the machinery that mediates genomic processes such as transcription, repair and replication. the cell solves this accessibility problem during double-strand dna repair by removing the histone proteins flanking the dna lesion. presumably then, the repaired dna is subsequently reassembled into chromatin in order to allow the epigenetic information to be restored and to repackage and protect the genome. our rece ... | 2008 | 19066448 |
| application of a c. elegans dopamine neuron degeneration assay for the validation of potential parkinson's disease genes. | improvements to the diagnosis and treatment of parkinson's disease (pd) are dependent upon knowledge about susceptibility factors that render populations at risk. in the process of attempting to identify novel genetic factors associated with pd, scientists have generated many lists of candidate genes, polymorphisms, and proteins that represent important advances, but these leads remain mechanistically undefined. our work is aimed toward significantly narrowing such lists by exploiting the advant ... | 2008 | 19066512 |
| scavenger receptor collectin placenta 1 (cl-p1) predominantly mediates zymosan phagocytosis by human vascular endothelial cells. | collectin placenta 1 (cl-p1), a recently discovered scavenger receptor, mediates the uptake of oxidized low density lipoprotein and microbes. in this study, we investigated cl-p1-mediated binding and ingestion of yeast-derived zymosan bioparticles using chinese hamster ovary (cho) cells stably expressing human cl-p1 (cho/cl-p1) and human vascular endothelial cells constitutively expressed cl-p1. the uptake of zymosan by cho/cl-p1 was dependent upon the level of cl-p1 expressed on the membrane an ... | 2009 | 19073604 |
| human rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes. | the rad52 protein has critical functions in distinct pathways of the homology-directed dna repair, one of which is to promote the annealing of complementary strands of dna. both yeast and human rad52 proteins organize into ring-shaped oligomers with the predominant form being a heptamer. despite the wealth of information obtained in previous investigations, how rad52 mediates homology search and annealing remains unclear. here, we developed single-molecule fluorescence resonance energy transfer ... | 2008 | 19074292 |
| functional rescue of mutant human cystathionine beta-synthase by manipulation of hsp26 and hsp70 levels in saccharomyces cerevisiae. | many human diseases are caused by missense substitutions that result in misfolded proteins that lack biological function. here we express a mutant form of the human cystathionine beta-synthase protein, i278t, in saccharomyces cerevisiae and show that it is possible to dramatically restore protein stability and enzymatic function by manipulation of the cellular chaperone environment. we demonstrate that hsp70 and hsp26 bind specifically to i278t but that these chaperones have opposite biological ... | 2009 | 19074437 |
| characterization and functional analysis of the beta-1,3-glucanosyltransferase 3 of the human pathogenic fungus paracoccidioides brasiliensis. | the fungus paracoccidioides brasiliensis causes paracoccidioidomycosis, a systemic granulomatous mycosis prevalent in latin america. in an effort to elucidate the molecular mechanisms involved in fungus cell wall assembly and morphogenesis, beta-1,3-glucanosyltransferase 3 (pbgel3p) is presented here. pbgel3p presented functional similarity to the glucan-elongating/glycophospholipid-anchored surface/ph-regulated /essential for pseudohyphal development protein families, which are involved in fung ... | 2009 | 19076240 |
| pancreatitis-associated protein inhibits human pancreatic stellate cell mmp-1 and -2, timp-1 and -2 secretion and reck expression. | pancreatic stellate cells (pscs) play a key role in fibrogenesis associated with acute and chronic pancreatitis. pancreatitis-associated protein (pap), an acute-phase protein, is dramatically upregulated during acute and chronic pancreatitis. assuming a protective role of pap, we investigated its effects on human pscs. | 2009 | 19077460 |
| directed evolution of estrogen receptor proteins with altered ligand-binding specificities. | transcriptional activators that respond to ligands with no cellular targets are powerful tools that can confer regulated expression of a transgene in almost all biological systems. in this study, we altered the ligand-binding specificity of the human estrogen receptor alpha (her alpha) so that it would recognize a non-steroidal synthetic compound with structural similarities to the phytoestrogen resveratrol. for this purpose, we performed iterative rounds of site-specific saturation mutagenesis ... | 2009 | 19088113 |
| [pityriasis versicolor and the yeasts of genus malassezia]. | although pityriasis versicolor is the only human disease for which malassezia yeasts have been fully established as pathogens, it is still not clear which species are implicated. most studies carried out in recent years support our hypothesis - proposed in 1999 - that malassezia globosa is the predominant species in pityriasis versicolor lesions, at least in temperate climates. confirmation of this hypothesis could help us understand the conditions, as yet unclear, that induce transformation of ... | 2008 | 19091214 |
| polar mapper: a computational tool for integrated visualization of protein interaction networks and mrna expression data. | polar mapper is a computational application for exposing the architecture of protein interaction networks. it facilitates the system-level analysis of mrna expression data in the context of the underlying protein interaction network. preliminary analysis of a human protein interaction network and comparison of the yeast oxidative stress and heat shock gene expression responses are addressed as case studies. | 2009 | 19091689 |
| research on animal model organisms funded by the european commission's framework programmes. | recognising the crucial role of model organisms in exploring the causes of human disease and in developing safe treatments, the european commission has invested euro180 million in collaborative research projects on model organisms since 2002. further financial support is planned for the future. projects supported by the european commission are playing an important role in structuring the research landscape in europe and creating the knowledge base to understand health and disease. furthermore, t ... | 2008 | 19093026 |
| papa-1 is a nuclear binding partner of igfbp-2 and modulates its growth-promoting actions. | igf-binding proteins (igfbps) have multiple cellular effects, which occur by both igf-dependent and -independent mechanisms. igfbp-2 is involved in the regulation of both normal and carcinogenic cell growth. to further understand the actions of igfbp-2, we carried out a yeast two-hybrid screen to search for intracellular partner proteins using a human prostate cdna library. we isolated pim-1-associated protein-1 (pap-1)-associated protein-1 (papa-1) as an igfbp-2-binding protein, whose expressio ... | 2009 | 19095771 |
| malleable machines in transcription regulation: the mediator complex. | the mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including rna polymerase ii (rnap ii). the complex has a modular architecture (head, middle, and tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and rnap ii. these rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to th ... | 2008 | 19096501 |
| the arabidopsis blap75/rmi1 homologue plays crucial roles in meiotic double-strand break repair. | in human cells and in saccharomyces cerevisiae, blap75/rmi1 acts together with blm/sgs1 and topoiiialpha/top3 to maintain genome stability by limiting crossover (co) formation in favour of nco events, probably through the dissolution of double holliday junction intermediates (dhj). so far, very limited data is available on the involvement of these complexes in meiotic dna repair. in this paper, we present the first meiotic study of a member of the blap75 family through characterisation of the ar ... | 2008 | 19096505 |
| atp-dependent unwinding of u4/u6 snrnas by the brr2 helicase requires the c terminus of prp8. | the spliceosome is a highly dynamic machine requiring multiple rna-dependent atpases of the dexd/h-box family. a fundamental unanswered question is how their activities are regulated. brr2 function is necessary for unwinding the u4/u6 duplex, a step essential for catalytic activation of the spliceosome. here we show that brr2-dependent dissociation of u4/u6 snrnas in vitro is activated by a fragment from the c terminus of the u5 snrnp protein prp8. in contrast to its helicase-stimulating activit ... | 2009 | 19098916 |
| mtor-what does it do? | target of rapamycin (tor) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. tor, which was originally discovered in yeast, is conserved in all eukaryotes including plants, worms, flies, and mammals. the discovery of tor led to a fundamental change in how we think about cell growth. it is not a spontaneous process that just happens when building blocks (nutrients) are available, but rather ... | 2008 | 19100909 |
| interaction of dengue virus envelope protein with endoplasmic reticulum-resident chaperones facilitates dengue virus production. | dengue virus infection is an important mosquito-borne disease and a public health problem worldwide. a better understanding of interactions between human cellular host and dengue virus proteins will provide insight into dengue virus replication and cellular pathogenesis. the glycosylated envelope protein of dengue virus, denv e, is processed in the endoplasmic reticulum of host cells and therefore reliant on host processing functions. the complement of host er functions involved and nature of th ... | 2009 | 19105951 |
| human polycomb 2 protein is a sumo e3 ligase and alleviates substrate-induced inhibition of cystathionine beta-synthase sumoylation. | human cystathionine beta-synthase (cbs) catalyzes the first irreversible step in the transsulfuration pathway and commits homocysteine to the synthesis of cysteine. mutations in cbs are the most common cause of severe hereditary hyperhomocysteinemia. a yeast two-hybrid approach to screen for proteins that interact with cbs had previously identified several components of the sumoylation pathway and resulted in the demonstration that cbs is a substrate for sumoylation. in this study, we demonstrat ... | 2008 | 19107218 |
| reproductive health of bass in the potomac, u.s.a., drainage: part 2. seasonal occurrence of persistent and emerging organic contaminants. | the seasonal occurrence of organic contaminants, many of which are potential endocrine disruptors, entering the potomac river, usa, watershed was investigated using a two-pronged approach during the fall of 2005 and spring of 2006. passive samplers (semipermeable membrane device and polar organic chemical integrative sampler [pocis]) were deployed in tandem at sites above and below wastewater treatment plant discharges within the watershed. analysis of the samplers resulted in detection of 84 of ... | 2009 | 19108592 |
| tax1bp1 interacts with papillomavirus e2 and regulates e2-dependent transcription and stability. | the papillomavirus e2 proteins regulate viral replication, gene transcription, and genome maintenance by interacting with other viral and host proteins. from a yeast two-hybrid screen, we identified the cellular protein tax1bp1 as a novel binding partner of human papillomavirus type 18 (hpv18) e2. tax1bp1 also interacts with the hpv16 and bovine papillomavirus type 1 (bpv1) e2 proteins, with the c-terminal region of tax1bp1 interacting with the n-terminal transactivation domain of bpv1 e2. tax1b ... | 2009 | 19109394 |
| spe-39 family proteins interact with the hops complex and function in lysosomal delivery. | yeast and animal homotypic fusion and vacuole protein sorting (hops) complexes contain conserved subunits, but hops-mediated traffic in animals might require additional proteins. here, we demonstrate that spe-39 homologues, which are found only in animals, are present in rab5-, rab7-, and rab11-positive endosomes where they play a conserved role in lysosomal delivery and probably function via their interaction with the core hops complex. although caenorhabditis elegans spe-39 mutants were initia ... | 2009 | 19109425 |
| translational control of bace1 may go awry in alzheimer's disease. | our understanding of the mechanisms whereby bace1, the aspartyl protease required for the initial cleavage of app to generate amyloid-beta (abeta), is regulated in alzheimer's disease (ad) remains incomplete. in this issue of neuron, o'connor and coworkers show how energy deprivation, a potential risk factor in ad, triggers the phosphorylation of the translation initiation factor eif2alpha to elevate the translation efficiency of a set of stress-related transcripts, including that of bace1, and ... | 2008 | 19109900 |
| homology modeling of human transketolase: description of critical sites useful for drug design and study of the cofactor binding mode. | transketolase, the most critical enzyme of the non-oxidative branch of the pentose phosphate pathway, has been reported as a new target protein for cancer research. however, since the crystal structure of human transketolase is unknown, no structure-based methods can be used to identify new inhibitors. we performed homology modeling of human transketolase using the crystal structure of yeast as a template, and then refined the model through molecular dynamics simulations. based on the resulting ... | 2009 | 19111488 |
| potentiation of amyotrophic lateral sclerosis (als)-associated tdp-43 aggregation by the proteasome-targeting factor, ubiquilin 1. | tdp-43 (43-kda tar dna-binding domain protein) is a major constituent of ubiquitin-positive cytoplasmic aggregates present in neurons of patients with fronto-temporal lobular dementia and amyotrophic lateral sclerosis (als). the pathologic significance of tdp-43 aggregation is not known; however, dominant mutations in tdp-43 cause a subset of als cases, suggesting that misfolding and/or altered trafficking of tdp-43 is relevant to the disease process. here, we show that the presenilin-binding pr ... | 2009 | 19112176 |
| akt regulates drug-induced cell death through bcl-w downregulation. | akt is a serine threonine kinase with a major role in transducing survival signals and regulating proteins involved in apoptosis. to find new interactors of akt involved in cell survival, we performed a two-hybrid screening in yeast using human full-length akt c-dna as bait and a murine c-dna library as prey. among the 80 clones obtained, two were identified as bcl-w. bcl-w is a member of the bcl-2 family that is essential for the regulation of cellular survival, and that is up-regulated in diff ... | 2008 | 19114998 |
| 3d imaging of mammalian cells with ion-abrasion scanning electron microscopy. | understanding the hierarchical organization of molecules and organelles within the interior of large eukaryotic cells is a challenge of fundamental interest in cell biology. we are using ion-abrasion scanning electron microscopy (ia-sem) to visualize this hierarchical organization in an approach that combines focused ion-beam milling with scanning electron microscopy. here, we extend our previous studies on imaging yeast cells to image subcellular architecture in human melanoma cells and melanoc ... | 2009 | 19116171 |
| chaperone-mediated autophagy is defective in mucolipidosis type iv. | mucolipidosis type iv (mliv) is a lysosomal storage disorder caused by mutations in the mcoln1 gene, a member of the transient receptor potential (trp) cation channel gene family. the encoded protein, transient receptor potential mucolipin-1 (trpml1), has been localized to lysosomes and late endosomes but the pathogenic mechanism by which loss of trpml1 leads to abnormal cellular storage and neuronal cell death is still poorly understood. yeast two-hybrid and co-immunoprecipitation (coip) experi ... | 2009 | 19117012 |
| mismatch oligonucleotides in human and yeast: guidelines for probe design on tiling microarrays. | mismatched oligonucleotides are widely used on microarrays to differentiate specific from nonspecific hybridization. while many experiments rely on such oligos, the hybridization behavior of various degrees of mismatch (mm) structure has not been extensively studied. here, we present the results of two large-scale microarray experiments on s. cerevisiae and h. sapiens genomic dna, to explore mm oligonucleotide behavior with real sample mixtures under tiling-array conditions. | 2008 | 19117516 |
| oxidosqualene cyclase from saccharomyces cerevisiae, trypanosoma cruzi, pneumocystis carinii and arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents. | a series of 25 compounds, some of which previously were described as inhibitors of human liver microsomal oxidosqualene cyclase (osc), were tested as inhibitors of saccharomyces cerevisiae, trypanosoma cruzi, pneumocystis carinii and arabidopsis thaliana oscs expressed in an osc-defective strain of s. cerevisiae. the screening identified three derivatives particularly promising for the development of novel anti-trypanosoma agents and eight derivatives for the development of novel anti-pneumocyst ... | 2009 | 19119009 |
| signalling pathway involving gulp, mapk and rac1 for sr-bi-induced phagocytosis of apoptotic cells. | class b scavenger receptor type i (sr-bi) is a phosphatidylserine (ps)-recognizing receptor of testicular sertoli cells responsible for the phagocytosis of spermatogenic cells undergoing apoptosis. here, we determined signal mediators that compose a signalling pathway for sr-bi-induced phagocytosis. results of a yeast two-hybrid analysis and a cell-free binding assay indicated that sr-bi binds to engulfment adapter protein (gulp) using the c-terminal intracellular domain. a co-immunoprecipitatio ... | 2009 | 19122200 |
| zinc finger transcription factor insm1 interrupts cyclin d1 and cdk4 binding and induces cell cycle arrest. | insm1 is a zinc finger transcription factor that plays an important role in pancreatic beta-cell development. to further evaluate its role in cell fate determination, we investigated insm1 effects on cell cycle function. the cyclin box of cyclin d1 is essential for insm1 binding. competitive pull-down and co-immunoprecipitation revealed that insm1 binding to cyclin d1 interrupts its association with cdk4 and induces hypophosphorylation of the retinoblastoma protein. an inducible tet-on system wa ... | 2009 | 19124461 |
| human trehalase is a stress responsive protein in saccharomyces cerevisiae. | three trehalases ath1, nth1, and nth2 have been identified in saccharomyces cerevisiae. ath1, and nth1 hydrolyze trehalose to glucose to provide energy and assist in recovery from stress. human trehalase (treh) is expressed in the intestine and kidney and probably hydrolyzes ingested trehalose in the intestine and acts as marker of renal tubular damage in kidney. since trehalose is not present in circulation or kidney tubules, its renal effect suggests it has other yet unidentified actions. here ... | 2009 | 19126402 |
| expression of two human acyl-coa:diacylglycerol acyltransferase isozymes in yeast and selectivity of microbial inhibitors toward the isozymes. | two isozymes for human acyl-coenzyme a:diacylglycerol acyltransferase (dgat), dgat1 and dgat2, were independently expressed in dgat-deficient saccharomyces cerevisiae to establish dgat1- and dgat2-s. cerevisiae. the selectivity of dgat inhibitors of natural origin towards the isozymes was assessed in enzyme assays using the microsomal fractions prepared from dgat1- and dgat2-s. cerevisiae. amidepsines and xanthohumol inhibited dgat1 and dgat2 with similar potency, whereas roselipins were found t ... | 2009 | 19132064 |
| a role of helix 12 of the vitamin d receptor in smrt corepressor interaction. | to repress gene transcription, the unliganded nuclear receptor (nr) recruits the n-cor and smrt corepressors via its direct association with the conserved motif within bipartite nr-interaction domains (ids) of corepressors. we recently reported that smrt is directly involved in the vdr-mediated repression via an id1-specific interaction with the vdr. here we show that removal of helix 12 from vdr (vdrdeltaaf2) converts it to a more potent repressor through additional interaction between the vdr ... | 2009 | 19133230 |
| superoxide dismutase is regulated by lammer kinase in drosophila and human cells. | lammer kinases (also known as cdc-2-like or clks) are a family of dual specificity serine/threonine protein kinases that are found in all sequenced eukaryotic genomes. in the fission yeast, schizosaccharomyces pombe, the lammer kinase gene, lkh1, positively regulates the expression of the antioxidant defense genes, superoxide dismutase 1 (sod1+, cuzn-sod) and catalase (ctt1+, cat). we have shown that mutations in the drosophila lammer kinase gene, darkener of apricot (doa), protect against the d ... | 2009 | 19135146 |
| human ribonuclease 9, a member of ribonuclease a superfamily, specifically expressed in epididymis, is a novel sperm-binding protein. | to explore the functions of human ribonuclease 9 (rnase 9), we constructed a mammalian fusion expression vector pcdna-hrnase9, prepared recombinant human rnase 9-his fusion protein from hek293t cells and determined its n-terminal amino acid sequences. according to the determined mature protein, recombinant human rnase 9 was prepared in e. coli. ribonucleolytic activity and antibacterial activity of recombinant human rnase 9 were detected, and the distribution of human rnase 9 on tissues and ejac ... | 2009 | 19137000 |
| hshroom1 links a membrane bound protein to the actin cytoskeleton. | hshroom1 (hshrm1) is a member of the apx/shroom (shrm) protein family and was identified from a yeast two-hybrid screen as a protein that interacts with the cytoplasmic domain of melanoma cell adhesion molecule (mcam). the characteristic signature of the shrm family is the presence of a unique domain, asd2 (apx/shroom domain 2). mrna analysis suggests that hshrm1 is expressed in brain, heart, skeletal muscle, colon, small intestine, kidney, placenta and lung tissue, as well a variety of melanoma ... | 2009 | 19137261 |
| the g67e mutation in hmlh1 is associated with an unusual presentation of lynch syndrome. | germline mutations in the mismatch repair (mmr) genes are associated with lynch syndrome, also known as hereditary non-polyposis colorectal cancer (hnpcc) syndrome. here, we characterise a variant of hmlh1 that confers a loss-of-function mmr phenotype. the mutation changes the highly conserved gly67 residue to a glutamate (g67e) and is reminiscent of the hmlh1-p.gly67arg mutation, which is present in several lynch syndrome cohorts. hmlh1-gly67arg has previously been shown to confer loss-of-funct ... | 2009 | 19142183 |
| evolution and assembly of escrts. | the aaa (atpase associated with various cellular activities) proteins participate in membrane trafficking, organelle biogenesis, dna replication, intracellular locomotion, cytoskeletal remodelling, protein folding and proteolysis. the aaa vps (vacuolar protein sorting) 4 is central to traffic to lysosomes, retroviral budding and mammalian cell division. it dissociates escrts (endosomal sorting complexes required for transport) from endosomal membranes, enabling their recycling to the cytosol, an ... | 2009 | 19143621 |
| yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing hiv-1 basal transcription. | rebound of hiv viremia after interruption of anti-retroviral therapy is due to the small population of cd4+ t cells that remain latently infected. hiv-1 transcription is the main process controlling post-integration latency. regulation of hiv-1 transcription takes place at both initiation and elongation levels. pausing of rna polymerase ii at the 5' end of hiv-1 transcribed region (5'hiv-tr), which is immediately downstream of the transcription start site, plays an important role in the regulati ... | 2009 | 19148280 |
| pharmaceutical strategies for activating sirtuins. | the sirtuins are protein modifying enzymes widely distributed in all forms of life. the sirtuins are principally nad(+)-dependent protein acetyl-lysine deacetylases that reverse acetyl-modifications of proteins. the sirtuins are implicated in a variety of adaptations to reduced nutritional intake, and increase lifespan in several model organisms, such as yeast, flies and worms. the human sirtuins (sirt1-7) have been identified to regulate a variety of biological processes, such as glucose homeos ... | 2009 | 19149602 |
| the protein-tyrosine kinase syk interacts with traf-interacting protein trip in breast epithelial cells. | the nonreceptor, protein-tyrosine kinase syk is a suppressor of breast cancer progression whose expression is inversely correlated with the invasive behavior of cancer cells. in contrast, syk has a positive function in murine mammary tumor virus-mediated tumorigenesis. a yeast two-hybrid screen using a library from human mammary gland identified tumor necrosis factor (tnf) receptor-associated factor-interacting protein (trip) as an syk-binding partner. this interaction is mediated by the c-termi ... | 2009 | 19151749 |
| solution structure of the dna binding domain of rice telomere binding protein rtbp1. | rtbp1 is a rice telomeric protein that binds to the duplex array of tttaggg repeats at chromosome ends. the dna binding domain of rtbp1 contains a myb-type dna binding motif and a highly conserved c-terminal myb extension that is unique to plant telomeric proteins. using an electrophoretic mobility shift assay, we identified the c-terminal 110-amino acid region (rtbp1(506-615)) as the minimal telomeric dna binding domain, suggesting that the myb extension is required for binding plant telomeric ... | 2009 | 19152316 |
| interaction between human papillomavirus type 5 e2 and polo-like kinase 1. | the e2 protein of the papillomavirus plays an essential role in the viral life cycle. through a yeast two-hybrid screening, human polo-like kinase 1 was found to interact with human papillomavirus type 5 e2. further characterization identified that the domains responsible for the interaction are the transactivation domain of hpv-5 e2 and the sequence between the kinase and the polo box domains of plk1. in vivo, plk1 and hpv-5 e2 are colocalized at the nuclear speckles. in the skin epithelium not ... | 2009 | 19152411 |
| topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in live cells with a fluorescent probe. | isoprenylcysteine carboxyl methyltransferase (icmt) is a highly conserved enzyme that methyl esterifies the alpha carboxyl group of prenylated proteins including ras and related gtpases. methyl esterification neutralizes the negative charge of the prenylcysteine and thereby increases membrane affinity. icmt is an integral membrane protein restricted to the endoplasmic reticulum (er). the saccharomyces cerevisiae ortholog, ste14p, traverses the er membrane six times. we used a novel fluorescent r ... | 2009 | 19158273 |
| all eukaryotes: before turning off g1-s transcription, please check your dna. | the dna replication and dna damage checkpoints are required for the efficient response to genotoxic stress, which is critical for genome stability and cell survival. the dna replication and damage checkpoints delay progression into mitosis, and at the same time induce the transcription of genes that promote repair of cellular lesions including stabilization of stalled replication forks and induction of dna repair functions. the elucidation of the mechanism by which the dna replication checkpoint ... | 2009 | 19158488 |
| regulation of interleukin-12/interleukin-23 production and the t-helper 17 response in humans. | interleukin-12 (il-12) and il-23 share a common chain. yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. il-12 is involved in the induction or amplification of the t-helper (th) type 1 response, whereas il-23 has been associated with the generation of the th17 response and il-17 production. mycobacterium tuberculosis and yeast zymosan induce il-23, but in the absence of other stimuli, no il-12 is induced in human de ... | 2008 | 19161420 |
| functional organization of the yeast proteome by a yeast interactome map. | it is hoped that comprehensive mapping of protein physical interactions will facilitate insights regarding both fundamental cell biology processes and the pathology of diseases. to fulfill this hope, good solutions to 2 issues will be essential: (i) how to obtain reliable interaction data in a high-throughput setting and (ii) how to structure interaction data in a meaningful form, amenable to and valuable for further biological research. in this article, we structure an interactome in terms of p ... | 2009 | 19164585 |
| prion and nonprion amyloids: a comparison inspired by the yeast sup35 protein. | yeast prion determinants are related to polymerization of some proteins into amyloid-like fibers. the [psi(+)] determinant reflects polymerization of the sup35 protein. fragmentation of prion polymers by the hsp104 chaperone represents a key step of the prion replication cycle. the frequency of fragmentation varies depending on the structure of the prion polymers and defines variation in the prion phenotypes, e.g., the suppressor strength of [psi(+)] and stability of its inheritance. besides [ps ... | 2007 | 19164899 |
| contactin-associated protein (caspr) 2 interacts with carboxypeptidase e in the cns. | to identify proteins interacting with the intracellular domain of the neural cell adhesion molecule contactin-associated protein 2 (caspr2), yeast two-hybrid screening was performed. we identified carboxypeptidase e (cpe) as a caspr2-interacting candidate protein. glutathione s-transferase pull-down and immunoprecipitation analyses indicated that caspr2 was associated with cpe in vitro and in vivo. both caspr2 and cpe were expressed predominantly in the cns. immunohistochemical analyses revealed ... | 2009 | 19166515 |
| an investigation of ribosomal protein l10 gene in autism spectrum disorders. | autism spectrum disorders (asd) are severe neurodevelopmental disorders with the male:female ratio of 4:1, implying the contribution of x chromosome genetic factors to the susceptibility of asd. the ribosomal protein l10 (rpl10) gene, located on chromosome xq28, codes for a key protein in assembling large ribosomal subunit and protein synthesis. two non-synonymous mutations of rpl10, l206m and h213q, were identified in four boys with asd. moreover, functional studies of mutant rpl10 in yeast exh ... | 2009 | 19166581 |
| structural and mechanistic analyses of yeast mitochondrial thioredoxin trx3 reveal putative function of its additional cysteine residues. | the yeast saccharomyces cerevisiae trx3 is a key member of the thioredoxin system to control the cellular redox homeostasis in mitochondria. we solved the crystal structures of yeast trx3 in oxidized and reduced forms at 1.80 and 2.10 a, respectively. besides the active site, the additional cysteine residue cys69 also undergoes a significant redox-correlated conformational change. comparative structural analyses in combination with activity assays revealed that residue cys69 could be s-nitrosyla ... | 2009 | 19166985 |
| polyubiquitin substrates allosterically activate their own degradation by the 26s proteasome. | the 26s proteasome degrades polyubiquitylated (polyub) proteins by an atp-dependent mechanism. here we show that binding of model polyub substrates to the 19s regulator of mammalian and yeast 26s proteasomes enhances the peptidase activities of the 20s proteasome about two-fold in a process requiring atp hydrolysis. monoubiquitylated proteins or tetraubiquitin alone exert no effect. however, 26s proteasomes from the yeast alpha3deltan open-gate mutant and the rpt2ya and rpt5ya mutants with impai ... | 2009 | 19169257 |
| the cosmic silence experiment: on the putative adaptive role of environmental ionizing radiation. | previously we reported that yeast and chinese hamster v79 cells cultured under reduced levels of background environmental ionizing radiation show enhanced susceptibility to damage caused by acute doses of genotoxic agents. reduction of environmental radiation dose rate was achieved by setting up an underground laboratory at laboratori nazionali del gran sasso, central italy. we now report on the extension of our studies to a human cell line. human lymphoblastoid tk6 cells were maintained under i ... | 2009 | 19169701 |