| neutralizing human monoclonal antibodies binding multiple serotypes of botulinum neurotoxin. | botulism, a disease of humans characterized by prolonged paralysis, is caused by botulinum neurotoxins (bonts), the most poisonous substances known. there are seven serotypes of bont (a-g) which differ from each other by 34-64% at the amino acid level. each serotype is uniquely recognized by polyclonal antibodies, which originally were used to classify serotypes. to determine if there existed monoclonal antibodies (mabs) capable of binding two or more serotypes, we evaluated the ability of 35 ye ... | 2010 | 21149386 |
| suicidal gene therapy in an nf-κb-controlled tumor environment as monitored by a secreted blood reporter. | the nuclear factor-κb (nf-κb) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. we have cloned a novel nf-κb-based reporter system (five tandem repeats of nf-κb responsive genomic element (nf; 14 bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (cu) as a therapeutic gene and t ... | 2010 | 21150937 |
| the mitotic arrest deficient protein mad2b interacts with the clathrin light chain a during mitosis. | although the mitotic arrest deficient protein mad2b (mad2l2) is thought to inhibit the anaphase promoting complex (apc) by binding to cdc20 and/or cdh1 (fzr1), its exact role in cell cycle control still remains to be established. | 2010 | 21152103 |
| effect of tin and lead chlorotriphenyl analogues on selected living cells. | three kinds of living cells, human embryonic kidney cells, saccharomyces cerevisiae, and escherichia coli, were tested for their sensitivity to chlorotriphenyltin and chlorotriphenyllead. the tin compound proved definitely more toxic than the lead derivative, particularly in the case of the human embryonic kidney cells devoid of any protective cell wall. electron paramagnetic resonance (epr) comparative studies carried out by using a natural model liposome system (egg yolk lecithin) confirmed co ... | 2010 | 21154756 |
| replication and transcription of human papillomavirus type 58 genome in saccharomyces cerevisiae. | to establish a convenient system for the study of human papillomavirus (hpv), we inserted a saccharomyces cerevisiae selectable marker, ura, into hpv58 genome and transformed it into yeast. | 2010 | 21156081 |
| identification and engineering of human variable regions that allow expression of stable single-chain t cell receptors. | single-chain antibody fragments (scfv), consisting of two linked variable regions (v(h) and v(l)), are a versatile format for engineering and as potential antigen-specific therapeutics. although the analogous format for t cell receptors (tcrs), consisting of two linked v regions (vα and vβ; referred to here as sctv), could provide similar opportunities, all wild-type sctv proteins examined to date are unstable. this obstacle has prevented sctv fragments from being widely used for engineering or ... | 2010 | 21159619 |
| activation of amyloid precursor protein processing by growth factors is dependent on ras gtpase activity. | the β-amyloid peptide is generated by the proteolysis of the amyloid precursor protein (app) by the action of β- and γ-secretase. the mechanisms underlying this process are poorly understood. using a cell-based reporter gene assay we analysed the possible signals and pathways that could be involved in app cleavage. we used the stable cell line hela ag that expresses the human app(695) fused with the yeast transcription factor gal4. this fusion protein is normally translocated into the plasma mem ... | 2010 | 21161594 |
| addressing trypsin bias in large scale (phospho)proteome analysis by size exclusion chromatography and secondary digestion of large post-trypsin peptides. | in the vast majority of bottom-up proteomics studies, protein digestion is performed using only mammalian trypsin. although it is clearly the best enzyme available, the sole use of trypsin rarely leads to complete sequence coverage, even for abundant proteins. it is commonly assumed that this is because many tryptic peptides are either too short or too long to be identified by rplc-ms/ms. we show through in silico analysis that 20-30% of the total sequence of three proteomes (schizosaccharomyces ... | 2010 | 21166477 |
| a set of aspartyl protease-deficient strains for improved expression of heterologous proteins in kluyveromyces lactis. | secretion of recombinant proteins is a common strategy for heterologous protein expression using the yeast kluyveromyces lactis. however, a common problem is degradation of a target recombinant protein by secretory pathway aspartyl proteases. in this study, we identified five putative pfam00026 aspartyl proteases encoded by the k. lactis genome. a set of selectable marker-free protease deletion mutants was constructed in the prototrophic k. lactis gg799 industrial expression strain background us ... | 2010 | 21166768 |
| a novel dual dbp5/ddx19 homologue from plasmodium falciparum requires q motif for activity. | helicases are ubiquitous essential enzymes which have significant role in the nucleic acid metabolism. using in silico approaches in the recent past we have identified a number of helicases in the plasmodium falciparum genome. in the present study we report purification and detailed characterization of a novel helicase from p. falciparum. our results indicate that this helicase is a homologue of dbp5 and ddx19 from yeast and human, respectively. the biochemical characterization shows that it con ... | 2010 | 21168450 |
| mixed hsp90-cochaperone complexes are important for the progression of the reaction cycle. | the chaperone cycle of heat shock protein-90 (hsp90) involves progression through defined complexes with different cochaperones. it is still enigmatic how the exchange of cochaperones is regulated. the first cochaperone entering the cycle is the hsp90 atpase inhibitor sti1 (hop in human), which later is replaced by a prolyl isomerase (ppiase) and p23. we found, unexpectedly, that one sti1 molecule is sufficient to completely inhibit the atpase of the hsp90 dimer. upon addition of a ppiase cochap ... | 2010 | 21170051 |
| isobase: a database of functionally related proteins across ppi networks. | we describe isobase, a database identifying functionally related proteins, across five major eukaryotic model organisms: saccharomyces cerevisiae, drosophila melanogaster, caenorhabditis elegans, mus musculus and homo sapiens. nearly all existing algorithms for orthology detection are based on sequence comparison. although these have been successful in orthology prediction to some extent, we seek to go beyond these methods by the integration of sequence data and protein-protein interaction (ppi) ... | 2011 | 21177658 |
| generation of rna/dna hybrids in genomic dna by transformation using rna-containing oligonucleotides. | synthetic short nucleic acid polymers, oligonucleotides (oligos), are the most functional and widespread tools of molecular biology. oligos can be produced to contain any desired dna or rna sequence and can be prepared to include a wide variety of base and sugar modifications. moreover, oligos can be designed to mimic specific nucleic acid alterations and thus, can serve as important tools to investigate effects of dna damage and mechanisms of repair. we found that thermo scientific dharmacon rn ... | 2010 | 21178953 |
| single-cell tracking with a reversing flow cytometer. | we have developed an instrument based on a flow cytometer platform that is capable of tracking individual, suspended cells over extended time periods. the instrument repeatedly moves in a capillary the same volume segment of fluid containing tens to hundreds of suspended cells through the focal point of a laser. individual cells are then tracked based on the timing of when they cross the laser, and cell properties are measured as in a conventional flow cytometer. because cells are repeatedly mea ... | 2011 | 21182184 |
| functional null mutations of msrb3 encoding methionine sulfoxide reductase are associated with human deafness dfnb74. | the dfnb74 locus for autosomal-recessive, nonsyndromic deafness segregating in three families was previously mapped to a 5.36 mb interval on chromosome 12q14.2-q15. subsequently, we ascertained five additional consanguineous families in which deafness segregated with markers at this locus and refined the critical interval to 2.31 mb. we then sequenced the protein-coding exons of 18 genes in this interval. the affected individuals of six apparently unrelated families were homozygous for the same ... | 2010 | 21185009 |
| a novel binding protein of single immunoglobulin il-1 receptor-related molecule: paralemmin-3. | previous studies have shown that single immunoglobulin il-1 receptor-related molecule (sigirr) is a negative regulator of toll-interleukin-1 receptor signaling. nevertheless, the molecular mechanism of the negatively regulatory effect of sigirr remains unknown. using a yeast two-hybrid screen, we identified paralemmin-3 (palm3) as a novel binding protein of sigirr. this interaction of sigirr with palm3 was confirmed by coimmunoprecipitation in mammalian cells. in addition, the palm3 mrna express ... | 2010 | 21187075 |
| methylation of histone h3 lysine 36 enhances dna repair by nonhomologous end-joining. | given its significant role in the maintenance of genomic stability, histone methylation has been postulated to regulate dna repair. histone methylation mediates localization of 53bp1 to a dna double-strand break (dsb) during homologous recombination repair, but a role in dsb repair by nonhomologous end-joining (nhej) has not been defined. by screening for histone methylation after dsb induction by ionizing radiation we found that generation of dimethyl histone h3 lysine 36 (h3k36me2) was the maj ... | 2010 | 21187428 |
| who's who in human recombination: brca2 and rad52. | | 2010 | 21189297 |
| disruption of a sirt1-dependent autophagy checkpoint in the prostate results in prostatic intraepithelial neoplasia lesion formation. | the sirtuin family of proteins (sirt) encode a group of evolutionarily conserved, nad-dependent histone deacetylases, involved in many biological pathways. sirt1, the human homologue of the yeast silent information regulator 2 (sir2) gene, deacetylates histones, p300, p53, and the androgen receptor. autophagy is required for the degradation of damaged organelles and long-lived proteins, as well as for the development of glands such as the breast and prostate. herein, homozygous deletion of the s ... | 2010 | 21189328 |
| miip, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis. | the migration and invasion inhibitory protein (miip) was initially discovered in a yeast two-hybrid screen for proteins that interact and inhibit the migration and invasion-promoting protein insulin-like growth factor binding protein 2 (igfbp2). recent studies have shown that miip not only modulates igfbp2 but also regulates microtubule by binding to and inhibiting hdac6, a class 2 histone deacetylase that deacetylates α-tubulin, heat-shock protein 90 (hsp90), and cortactin. in addition, miip al ... | 2011 | 21190522 |
| telomere protein complexes and interactions with telomerase in telomere maintenance. | telomeres are the termini of linear chromosomes. they are composed of dna and dna-binding proteins critical for maintaining chromosome integrity and cellular function. telomere binding proteins regulate the structure and function of telomeres through the formation of different complexes with telomeric dna. double- and single-stranded telomeric dna binding protein complexes have shared and unique functions that regulate telomere homeostasis. recent studies have shown that telomerase interacts wit ... | 2011 | 21196166 |
| recombinant yeast technology at the cutting edge: robust tools for both designed catalysts and new biologicals. | health and safety concerns, enhanced quality criteria, and environmental sustainability, have prompted investigations into production using recombinant yeasts as a feasible alternative for isolation of proteins from natural animal or plant sources, as well as for processes utilising either mammalian cell cultures or bacterial systems. an overview of recent research papers and review articles provides readers with a comprehensive insight into the field of next-generation yeast expression systems. ... | 2010 | 21197847 |
| mutation to bax beyond the bh3 domain disrupts interactions with pro-survival proteins and promotes apoptosis. | pro-survival members of the bcl-2 family of proteins restrain the pro-apoptotic activity of bax, either directly through interactions with bax or indirectly by sequestration of activator bh3-only proteins, or both. mutations in bax that promote apoptosis can provide insight into how bax is regulated. here, we describe crystal structures of the pro-survival proteins mcl-1 and bcl-x(l) in complex with a 34-mer peptide from bax that encompasses its bh3 domain. these structures reveal canonical inte ... | 2011 | 21199865 |
| targeted amino-terminal acetylation of recombinant proteins in e. coli. | one major limitation in the expression of eukaryotic proteins in bacteria is an inability to post-translationally modify the expressed protein. amino-terminal acetylation is one such modification that can be essential for protein function. by co-expressing the fission yeast natb complex with the target protein in e.coli, we report a simple and widely applicable method for the expression and purification of functional n-terminally acetylated eukaryotic proteins. | 2010 | 21203426 |
| interaction of hsp40 with influenza virus m2 protein: implications for pkr signaling pathway. | influenza virus contains three integral membrane proteins: haemagglutinin, neuraminidase, and matrix protein (m1 and m2). among them, m2 protein functions as an ion channel, important for virus uncoating in endosomes of virus-infected cells and essential for virus replication. in an effort to explore potential new functions of m2 in the virus life cycle, we used yeast two-hybrid system to search for m2-associated cellular proteins. one of the positive clones was identified as human hsp40/hdj1, a ... | 2010 | 21204021 |
| candida albicans sfl2, a temperature-induced transcriptional regulator, is required for virulence in a murine gastrointestinal infection model. | many transcriptional regulators play roles in morphogenesis of the human pathogen candida albicans. recently, sfl2, a sequence homolog of c. albicans sfl1, has been shown to be required for hyphal development. in this report, we show that, like sfl1, sfl2 could complement the phenotypes of the saccharomyces cerevisiae sfl1 mutant, and green fluorescent protein-tagged sfl2 localized in the nuclei of both yeast and hyphal cells in c. albicans, reflecting its role as a transcriptional regulator. in ... | 2011 | 21205158 |
| phosphorylation of ulk1 (hatg1) by amp-activated protein kinase connects energy sensing to mitophagy. | adenosine monophosphate-activated protein kinase (ampk) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. in a screen for conserved substrates of ampk, we identified ulk1 and ulk2, mammalian orthologs of the yeast protein kinase atg1, which is required for autophagy. genetic analysis of ampk or ulk1 in mammalian liver and caenorhabditis elegans revealed a requirement for these kinases in autophagy. in mammals, loss of ampk ... | 2010 | 21205641 |
| the structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase pp2a. | leucine carboxyl methyltransferase 1 (lcmt1) methylates the terminal carboxyl group of the leucine 309 residue of human protein phosphatase 2a (pp2a). pp2a, a key regulator of many cellular processes, has recently generated additional interest as a potential cancer-therapeutic target. the status of pp2a methylation impacts upon the selection of the regulatory subunit by the pp2a core enzyme, thus directing its activity and subcellular localization. an x-ray crystal structure of human lcmt1 prote ... | 2010 | 21206058 |
| importin α/β mediates nuclear import of individual sumo e1 subunits and of the holo-enzyme. | sumoylation, reversible attachment of small ubiquitin-related modifier (sumo), serves to regulate hundreds of proteins. consistent with predominantly nuclear targets, enzymes required for attachment and removal of sumo are highly enriched in this compartment. this is true also for the first enzyme of the sumoylation cascade, the sumo e1 enzyme heterodimer, aos1/uba2 (sae1/sae2). this essential enzyme serves to activate sumo and to transfer it to the e2-conjugating enzyme ubc9. although the last ... | 2011 | 21209321 |
| role of the ubiquitin-like protein urm1 as a noncanonical lysine-directed protein modifier. | the ubiquitin (ub)-related modifier urm1 functions as a sulfur carrier in trna thiolation by means of a mechanism that requires the formation of a thiocarboxylate at the c-terminal glycine residue of urm1. however, whether urm1 plays an additional role as a ub-like protein modifier remains unclear. here, we show that urm1 is conjugated to lysine residues of target proteins and that oxidative stress enhances protein urmylation in both saccharomyces cerevisiae and mammalian cells. similar to ubiqu ... | 2011 | 21209336 |
| ubiquitin-dependent proteasomal degradation of human liver cytochrome p450 2e1: identification of sites targeted for phosphorylation and ubiquitination. | human liver cyp2e1 is a monotopic, endoplasmic reticulum-anchored cytochrome p450 responsible for the biotransformation of clinically relevant drugs, low molecular weight xenobiotics, carcinogens, and endogenous ketones. cyp2e1 substrate complexation converts it into a stable slow-turnover species degraded largely via autophagic lysosomal degradation. substrate decomplexation/withdrawal results in a fast turnover cyp2e1 species, putatively generated through its futile oxidative cycling, that inc ... | 2011 | 21209460 |
| crystal structure of uba2(ufd)-ubc9: insights into e1-e2 interactions in sumo pathways. | canonical ubiquitin-like proteins (ubls) such as ubiquitin, sumo, nedd8, and isg15 are ligated to targets by e1-e2-e3 multienzyme cascades. the sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, dna replication, and mitosis. sumo conjugation is initiated by the heterodimeric aos1-uba2 e1 enzyme (in humans called sae1-uba2), which activates sumo's c-terminus, binds the dedicated e2 enzyme ubc9, and promotes sumo c-t ... | 2010 | 21209884 |
| selected reaction monitoring by linear ion-trap mass spectrometry can effectively be applicable to simultaneous quantification of multiple peptides. | selected reaction monitoring (srm) mass spectrometry (ms) is becoming a popular approach for targeted quantitative proteomics. triple-quadrupole mass spectrometers have been historically considered as the instrument of choice for this type of quantitative analysis. recently, however, it has been reported that the srm ms with a linear ion-trap (lit) mass spectrometer is rather more appropriate for quantitative analysis of large peptides than the triple-quadrupole ones. in this study, we demonstra ... | 2011 | 21212531 |
| a combinatorial genetic library approach to target heterologous glycosylation enzymes to the endoplasmic reticulum or the golgi apparatus of pichia pastoris. | to humanize the glycosylation pathway in the yeast pichia pastoris, we developed several combinatorial genetic libraries and used them to properly localize active eukaryotic mannosidases and sugar transferases. here we report the details of the fusion of up to 66 n-terminal targeting sequences of fungal type ii membrane proteins to 33 catalytic domains of heterologous glycosylation enzymes. we show that while it is difficult to predict which leader/catalytic domain will result in the desired act ... | 2010 | 21213235 |
| a role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. | oxysterol-binding protein (osbp) and its related proteins (orps) constitute a large and evolutionarily conserved family of lipid-binding proteins that target organelle membranes to mediate sterol signaling and/or transport. here we characterize orp5, a tail-anchored orp protein that localizes to the endoplasmic reticulum. knocking down orp5 causes cholesterol accumulation in late endosomes and lysosomes, which is reminiscent of the cholesterol trafficking defect in niemann pick c (npc) fibroblas ... | 2011 | 21220512 |
| infection acquisition following intensive care unit room privatization. | patients in intensive care units (icus) often acquire infections, which impose a heavy human and financial burden. the use of private rooms may reduce the acquisition of certain pathogens, but the limited evidence on this topic is inconsistent. | 2011 | 21220658 |
| metabolic pathways of ochratoxin a. | ochratoxin a (ota) as a carcinogenic of group 2b to humans is produced by various fungi strains as aspergillus and penicillium. it is one of the most common contaminant in foodstuff. ota is nephrotoxic, hepatotoxic, teratogenic, and immunotoxic and is assumed to cause balkan endemic nephropathy (ben), a chronic kidney disease in humans when it is digested in combination with mycotoxin citrinin. the metabolism affects greatly the fates and the toxicity of a mycotoxins in humans, animals, and plan ... | 2011 | 21222585 |
| comparative genomics of proteins involved in rna nucleocytoplasmic export. | the establishment of the nuclear membrane resulted in the physical separation of transcription and translation, and presented early eukaryotes with a formidable challenge: how to shuttle rna from the nucleus to the locus of protein synthesis. in prokaryotes, mrna is translated as it is being synthesized, whereas in eukaryotes mrna is synthesized and processed in the nucleus, and it is then exported to the cytoplasm. in metazoa and fungi, the different rna species are exported from the nucleus by ... | 2011 | 21223572 |
| peptides and aptamers targeting hsp70: a novel approach for anticancer chemotherapy. | the inhibition of heat shock protein 70 (hsp70) is an emerging strategy in cancer therapy. unfortunately, no specific inhibitors are clinically available. by yeast two-hybrid screening, we have identified multiple peptide aptamers that bind hsp70. when expressed in human tumor cells, two among these peptide aptamers-a8 and a17-which bind to the peptide-binding and the atp-binding domains of hsp70, respectively, specifically inhibited the chaperone activity, thereby increasing the cells' sensitiv ... | 2011 | 21224349 |
| defining potentially conserved rna regulons of homologous zinc-finger rna-binding proteins. | abstract: background: glucose inhibition of gluconeogenic growth suppressor 2 protein (gis2p) and zinc-finger protein 9 (znf9) are conserved yeast and human zinc-finger proteins. the function of yeast gis2p is unknown, but human znf9 has been reported to bind nucleic acids, and mutations in the znf9 gene cause the neuromuscular disease myotonic dystrophy type 2. to explore the impact of these proteins on rna regulation, we undertook a systematic analysis of the rna targets and of the global impl ... | 2011 | 21232131 |
| a comprehensive study of tp53 mutations in chronic lymphocytic leukemia: analysis of 1287 diagnostic and 1148 follow-up cll samples. | tp53 plays a pivotal role in the process of dna repair and apoptosis. in 10-20% of patients with chronic lymphocytic leukemia (cll), the tp53 pathway is affected. in this study, we analyzed the tp53 mutation status in 2435 consecutive cll samples, including 1287 diagnostic samples and 1148 samples during follow-up, using fasay (functional analysis of separated alleles in yeast) and direct sequencing. in a cohort of 1287 diagnostic cll samples, we identified 237 cases with tp53 variants, includin ... | 2011 | 21232794 |
| human cdc14a becomes a cell cycle gene in controlling cdk1 activity at the g₂/m transition. | cdc14 belongs to a dual-specificity phosphatase family highly conserved through evolution that preferentially reverses cdk (cyclin dependent kinases) -dependent phosphorylation events. in the yeast saccharomyces cerevisiae, cdc14 is an essential regulator of late mitotic events and exit from mitosis by counteracting cdk activity at the end of mitosis. however, many studies have shown that cdc14 is dispensable for exiting mitosis in all other model systems analyzed. in fission yeast, the cdc14 ho ... | 2011 | 21233601 |
| structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease. | the attachment of ubiquitin (ub) and the ub-like (ubl) molecule interferon-stimulated gene 15 (isg15) to cellular proteins mediates important innate antiviral responses. ovarian tumor (otu) domain proteases from nairoviruses and arteriviruses were recently found to remove these molecules from host proteins, which inhibits ub and isg15-dependent antiviral pathways. this contrasts with the ub-specific activity of known eukaryotic otu-domain proteases. here we describe crystal structures of a viral ... | 2011 | 21245344 |
| the chaperone network connected to human ribosome-associated complex. | mammalian ribosome-associated complex (mrac), consisting of the j-domain protein mpp11 and the atypical hsp70 homolog (70-homolog) hsp70l1, can partly complement the function of rac, which is the homologous complex from saccharomyces cerevisiae. rac is the j-domain partner exclusively of the 70-homolog ssb, which directly and independently of rac binds to the ribosome. we here show that growth defects due to mrac depletion in hela cells resemble those of yeast strains lacking rac. functional con ... | 2011 | 21245388 |
| ubiquitin-proteasome genes as targets for modulation of cisplatin sensitivity in fission yeast. | the ubiquitin(ub)-proteasome pathway is implicated in the regulation of a variety of cellular functions and plays a major role in stress response in eukaryotic cells, by targeting misfolded and damaged proteins for degradation. in addition, in the presence of dna damage, the ub-proteasome system regulates proteins involved in sensing, repairing, and/or tolerating the damage. antitumor agents such as cisplatin can activate the pathway, but the role of specific pathway components in cell sensitivi ... | 2011 | 21247416 |
| a simple model for the influence of meiotic conversion tracts on gc content. | a strong correlation between gc content and recombination rate is observed in many eukaryotes, which is thought to be due to conversion events linked to the repair of meiotic double-strand breaks. in several organisms, the length of conversion tracts has been shown to decrease exponentially with increasing distance from the sites of meiotic double-strand breaks. i show here that this behavior leads to a simple analytical model for the evolution and the equilibrium state of the gc content of sequ ... | 2011 | 21249197 |
| tbc proteins: gaps for mammalian small gtpase rab? | the tbc (tre-2/bub2/cdc16) domain was originally identified as a conserved domain among the tre-2 oncogene product and the yeast cell cycle regulators bub2 and cdc16, and it is now widely recognized as a conserved protein motif that consists of approx. 200 amino acids in all eukaryotes. since the tbc domain of yeast gyps [gap (gtpase-activating protein) for ypt proteins] has been shown to function as a gap domain for small gtpase ypt/rab, tbc domain-containing proteins (tbc proteins) in other sp ... | 2011 | 21250943 |
| expression of water-soluble, ligand-binding concatameric extracellular domains of the human neuronal nicotinic receptor alpha4 and beta2 subunits in the yeast pichia pastoris: glycosylation is not required for ligand binding. | nicotinic acetylcholine receptors (nachrs) are ligand-gated cation channels that are responsible for cell communication via the neurotransmitter acetylcholine. the predominant nachr subtype in the mammalian brain with a high affinity for nicotine is composed of a4 and ß2 subunits. this nachr subtype is responsible for addiction to nicotine and is thought to be implicated in alzheimer and parkinson diseases and therefore presents an important target for drug design. in an effort to obtain water-s ... | 2011 | 21252231 |
| a mutation in the gene encoding mitochondrial mg²+ channel mrs2 results in demyelination in the rat. | the rat demyelination (dmy) mutation serves as a unique model system to investigate the maintenance of myelin, because it provokes severe myelin breakdown in the central nervous system (cns) after normal postnatal completion of myelination. here, we report the molecular characterization of this mutation and discuss the possible pathomechanisms underlying demyelination. by positional cloning, we found that a g-to-a transition, 177 bp downstream of exon 3 of the mrs2 (mrs2 magnesium homeostasis fa ... | 2011 | 21253565 |
| glycosylation status of the c. albicans cell wall affects the efficiency of neutrophil phagocytosis and killing but not cytokine signaling. | the cell wall of the opportunistic human fungal pathogen, candida albicans is a complex, layered network of rigid structural polysaccharides composed of β-glucans and chitin that is covered with a fibrillar matrix of highly glycosylated mannoproteins. polymorphonuclear cells (pmns, neutrophils) are the most prevalent circulating phagocytic leukocyte in peripheral blood and they are pivotal in the clearance of invading fungal cells from tissues. the importance of cell-wall mannans for the recogni ... | 2011 | 21254968 |
| a novel neuron-enriched protein sdim1 is down regulated in alzheimer's brains and attenuates cell death induced by dnajb4 over-expression in neuro-progenitor cells. | | 2011 | 21255413 |
| (1→3)-β-d-glucan inhibits a dual mechanism of peroxynitrite stroke. | the antioxidative and antinitrative activities of (1→3)-β-d-glucan (1-4μg/ml) from the yeast cell walls of saccharomyces cerevisiae in human plasma treated with strong oxidants - peroxynitrite (onoo(-)) (0.1mm) and hydrogen peroxide (h(2)o(2)) (2mm) were studied in vitro. the main purpose of this study was to assess if (1→3)-β-d-glucan, a well known strong immunostimulatory agent, possesses a protective function against dual mechanism of onoo(-) stroke associated with nitrative and oxidative dam ... | 2011 | 21255603 |
| microrna expression patterns of the kidney in hyperuricemia mice treated with xiezhuo chubi decoction. | to investigate the effects of xiezhuo chubi decoction (xzcbd) on the microrna expression patterns of kidney in mice with hyperuricemia. | 2011 | 21258895 |
| biclustering of gene expression data by correlation-based scatter search. | | 2011 | 21261986 |
| shox interacts with the chondrogenic transcription factors sox5 and sox6 to activate the aggrecan enhancer. | shox (short stature homeobox-containing gene) encodes a transcription factor implicated in skeletal development. shox haploinsufficiency has been demonstrated in leri-weill dyschondrosteosis (lwd), a skeletal dysplasia associated with disproportionate short stature, as well as in a variable proportion of cases with idiopathic short stature (iss). in order to gain insight into the shox signalling pathways, we performed a yeast two-hybrid screen to identify shox-interacting proteins. two transcrip ... | 2011 | 21262861 |
| rna polymerase i-specific subunits promote polymerase clustering to enhance the rrna gene transcription cycle. | rna polymerase i (pol i) produces large ribosomal rnas (rrnas). in this study, we show that the rpa49 and rpa34 pol i subunits, which do not have counterparts in pol ii and pol iii complexes, are functionally conserved using heterospecific complementation of the human and schizosaccharomyces pombe orthologues in saccharomyces cerevisiae. deletion of rpa49 leads to the disappearance of nucleolar structure, but nucleolar assembly can be restored by decreasing ribosomal gene copy number from 190 to ... | 2011 | 21263028 |
| pulmonary candidiasis presenting as mycetoma. | candida is a saprophytic yeast that is frequently recovered from the respiratory tract. most mycetoma lesions are due to aspergillus species growing inside an existing cavity. the saprophytic nature of the candida species in the human respiratory tract obscures diagnosis of candida pulmonary infections. only a few cases of mycetoma due to can-dida have been reported. we report a case of mycetoma caused by candida albicans in a diabetic immunocompromised tuberculous patient. diagnosis was confirm ... | 2008 | 21264087 |
| role of the interface between the fmn and fad domains in the control of redox potential and electronic transfer of nadph-cytochrome p450 reductase. | cpr (nadph-cytochrome p450 reductase) is a multidomain protein containing two flavin-containing domains joined by a connecting domain thought to control the necessary movements of the catalytic domains during electronic cycles. we present a detailed biochemical analysis of two chimaeric cprs composed of the association of human or yeast fmn with the alternative connecting/fad domains. despite the assembly of domains having a relatively large evolutionary distance between them, our data support t ... | 2011 | 21265736 |
| surface display of human lactoferrin using a glycosylphosphatidylinositol-anchored protein of saccharomyces cerevisiae in pichia pastoris. | a cell surface display system was developed in pichia pastoris using the gene tip1, encoding the glycosylphosphatidylinositol (gpi)-anchored protein of saccharomyces cerevisiae (sctip). human lactoferrin cdna (hlf) was fused to a full-length tip1 dna (sctip ( 630 )) or a short-tip1 fragment (sctip ( 120 )) encoding the 40 c-terminal amino acids of sctip. both hlf-sctip fusion genes were expressed in p. pastoris smd 1168. the fused protein was detected by western blotting after extraction of the ... | 2011 | 21267758 |
| rad52 function prevents chromosome loss and truncation in candida albicans. | rad52 is required for almost all recombination events in saccharomyces cerevisiae. we took advantage of the heterozygosity of his4 in the candida albicans sc5314 lineage to study the role of rad52 in the genomic stability of this important fungal pathogen. the rate of loss of heterozygosity (loh) at his4 in rad52-?? strains was ~10(-3) , at least 100-fold higher than in rad52(+) strains. loh of whole chromosome 4 or truncation of the homologue that carries the functional his4 allele was detected ... | 2011 | 21272099 |
| dissection of the relative contribution of the schizosaccharomyces pombe ctr4 and ctr5 proteins to the copper transport and cell surface delivery functions. | the ctr1 family of proteins mediates high-affinity copper (cu) acquisition in eukaryotic organisms. in the fission yeast schizosaccharomyces pombe, cu uptake is carried out by a heteromeric complex formed by the ctr4 and ctr5 proteins. unlike human and saccharomyces cerevisiae ctr1 proteins, ctr4 and ctr5 are unable to function independently in cu acquisition. instead, both proteins physically interact with each other to form a ctr4-ctr5 heteromeric complex, and are interdependent for secretion ... | 2011 | 21273250 |
| cell biology. why starving cells eat themselves. | | 2011 | 21273476 |
| saccharomyces cerevisiae gis2 interacts with the translation machinery and is orthogonal to myotonic dystrophy type 2 protein znf9. | the myotonic dystrophy type 2 protein znf9/cnbp is a small nucleic acid binding protein proposed to act as a regulator of transcription and translation. the precise functions and activity of this protein are poorly understood. previous studies suggested that znf9 regulates translation and facilitates the process of cap-independent translation through interactions with mrna and the translating ribosome. to help determine the role played by znf9 in the activation of translation initiation, we comb ... | 2011 | 21277287 |
| preparation of cho cell-derived rhifn-?-fc with improved pharmacokinetics. | interferon-omega (ifn-?) may be a useful, promising and alternative antiviral agent, in addition to ifn-a-2a and ifn-a-2b. to improve the pharmacokinetics of ifn-? for clinical use, the recombinant human ifn-?-fc fusion protein (rhifn-?-fc) was expressed in a chinese hamster ovary cell line (cho-s), due to the longer serum half-life of rhifn-?-fc compared to the native ifn-? protein, and purified by affinity chromatography. physicochemical characterization of the purified fusion protein was perf ... | 2011 | 21277904 |
| tyrosine 656 in topoisomerase iiß is important for the catalytic activity of the enzyme: identification based on artifactual +80-da modification at this site. | topoisomerase (topo) ii catalyzes topological changes in dna. although both human isozymes, topo iia and ß are phosphorylated, site-specific phosphorylation of topo iiß is poorly characterized. using lc-ms/ms analysis of topo iiß, cleaved with trypsin, arg c or cyanogen bromide (cnbr) plus trypsin, we detected four +80-da modified sites: tyr656, ser1395, thr1426 and ser1545. phosphorylation at ser1395, thr1426 and ser1545 was established based on neutral loss of h(3) po(4) (-98?da) in the cid sp ... | 2011 | 21280220 |
| cellular functions of ufd2 and ufd3 in proteasomal protein degradation depend on cdc48 binding. | the chaperone-related aaa atpase cdc48 (p97/vcp in higher eukaryotes) segregates ubiquitylated proteins for subsequent degradation by the 26s proteasome or for nonproteolytic fates. the specific outcome of cdc48 activity is controlled by the evolutionary conserved cofactors ufd2 and ufd3, which antagonistically regulate the substrates' ubiquitylation states. in contrast to the interaction of ufd3 and cdc48, the interaction between the ubiquitin chain elongating enzyme ufd2 and cdc48 has not been ... | 2011 | 21282470 |
| expansions, contractions, and fragility of the spinocerebellar ataxia type 10 pentanucleotide repeat in yeast. | spinocerebellar ataxia 10 (sca10) is an autosomal dominant disease caused by large-scale expansions of the (attct)(n) repeat within an intron of the human atxn10 gene. in contrast to other expandable repeats, this pentanucleotide repeat does not form stable intra- or interstranded dna structures, being a dna unwinding element instead. we analyzed the instability of the (attct)(n) repeat in a yeast experimental system, where its expansions led to inactivation of the ura3 reporter gene. the inacti ... | 2011 | 21282659 |
| cryptococcal osteomyelitis of the skull. | an otherwise healthy 65-year-old male from a rural area presented with a 1-month old non-tender scalp mass. he had a history of being stuck with a stone in the parietal region a year earlier but hadn't developed any complications. needle aspiration of the mass revealed numerous yeast cells, which were confirmed to be cryptoccus neoformans. this case describes a rare presentation of c. neoformans infection in a human immunodeficiency virus (hiv)-negative patient. moreover, while osteomyelitis due ... | 2011 | 21284568 |
| zinc-finger protein 90 negatively regulates neuron-restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes. | neuron-restrictive silencer factor (nrsf) is a zinc-finger transcription factor that binds to specific dna sequences (nrse) to repress transcription. by down-regulating the transcription of its target genes, nrsf contributes to the regulation of various biological processes, including neuronal differentiation, carcinogenesis and cardiovascular homeostasis. we previously reported that nrsf regulates expression of the cardiac fetal gene program, and that attenuation of nrsf-mediated repression con ... | 2011 | 21284946 |
| allele-specific effects of thoracic aortic aneurysm and dissection alpha-smooth muscle actin mutations on actin function. | twenty-two missense mutations in acta2, which encodes a-smooth muscle actin, have been identified to cause thoracic aortic aneurysm and dissection. limited access to diseased tissue, the presence of multiple unresolvable actin isoforms in the cell, and lack of an animal model have prevented analysis of the biochemical mechanisms underlying this pathology. we have utilized actin from the yeast saccharomyces cerevisiae, 86% identical to human a-smooth muscle actin, as a model. two of the known hum ... | 2011 | 21288906 |
| nutrient stress does not cause retrograde transport of cytoplasmic trna to the nucleus in evolutionarily diverse organisms. | intracellular trafficking of trna was long thought to be a one-way trip from the site of biogenesis in the nucleus to the translation machinery in the cytoplasm. this view has recently been challenged, however, by the discovery that trna can move retrograde from the cytoplasm back to the nucleus in saccharomyces cerevisiae and rat hepatoma h4iie cells during nutrient stress and in s. cerevisiae after intron-containing pre-trnas are spliced in the cytoplasm. contrary to studies reported, we prese ... | 2011 | 21289100 |
| the incorporation of 5-fluorouracil into rna affects the ribonucleolytic activity of the exosome subunit rrp6. | 5-fluorouracil (5fu) is a fluoropyrimidine used for the treatment of solid tumors. 5fu is a precursor of dttp and utp during biogenesis, and it interferes with both dna and rna metabolism. the rna exosome, a multisubunit complex with ribonucleolytic activity, has been identified as one of the targets of 5fu in yeast. studies in human cells have shown that the catalytic subunit of the nuclear exosome, rrp6, is specifically targeted. here, we have investigated the direct effect of 5fu on the activ ... | 2011 | 21289297 |
| resilience of protein-protein interaction networks as determined by their large-scale topological features. | the relationship between the structure and function of biological networks constitutes a fundamental issue in systems biology. particularly, the structure of protein-protein interaction networks is related to important biological functions. in this work, we investigated how such a resilience is determined by the large scale features of the respective networks. four species are taken into account, namely yeast saccharomyces cerevisiae, worm caenorhabditis elegans, fly drosophila melanogaster and ... | 2011 | 21298132 |
| simulating and validating proteomics data and search results. | the computational simulation of complete proteomic data sets and their utility to validate detection and interpretation algorithms, to aid in the design of experiments and to assess protein and peptide false discovery rates is presented. the simulation software has been developed for emulating data originating from data-dependent and data-independent lc-ms workflows. data from all types of commonly used hybrid mass spectrometers can be simulated. the algorithms are based on empirically derived p ... | 2011 | 21298790 |
| psm3 acetylation on conserved lysine residues is dispensable for viability in fission yeast but contributes to eso1-mediated sister chromatid cohesion by antagonizing wpl1. | in budding yeast and humans, cohesion establishment during s phase requires the acetyltransferase eco1/esco1-2, which acetylates the cohesin subunit smc3 on two conserved lysine residues. whether smc3 is the sole eco1/esco1-2 effector and how smc3 acetylation promotes cohesion are unknown. in fission yeast (schizosaccharomyces pombe), as in humans, cohesin binding to g(1) chromosomes is dynamic and the unloading reaction is stimulated by wpl1 (human ortholog, wapl). during s phase, a subpopulati ... | 2011 | 21300781 |
| subunit organization of the human ino80 chromatin remodeling complex: an evolutionarily conserved core complex catalyzes atp-dependent nucleosome remodeling. | we previously identified and purified a human atp-dependent chromatin remodeling complex with similarity to the saccharomyces cerevisiae ino80 complex (jin, j., cai, y., yao, t., gottschalk, a. j., florens, l., swanson, s. k., gutierrez, j. l., coleman, m. k., workman, j. l., mushegian, a., washburn, m. p., conaway, r. c., and conaway, j. w. (2005) j. biol. chem. 280, 41207-41212) and demonstrated that it is composed of (i) a snf2 family atpase (hino80) related in sequence to the s. cerevisiae i ... | 2011 | 21303910 |
| accurate quantification of functional analogy among close homologs. | correctly evaluating functional similarities among homologous proteins is necessary for accurate transfer of experimental knowledge from one organism to another, and is of particular importance for the development of animal models of human disease. while the fact that sequence similarity implies functional similarity is a fundamental paradigm of molecular biology, sequence comparison does not directly assess the extent to which two proteins participate in the same biological processes, and has l ... | 2011 | 21304936 |
| requirement for acetyl-coa carboxylase in trypanosoma brucei is dependent upon the growth environment. | trypanosoma brucei, the causative agent of human african trypanosomiasis, possesses two fatty acid synthesis pathways: a major de novo synthesis pathway in the er and a mitochondrial pathway. the 2-carbon donor for both pathways is malonyl-coa, which is synthesized from acetyl-coa by acetyl-coa carboxylase (acc). here, we show that t. brucei acc shares the same enzyme architecture and moderate ~ 30% identity with yeast and human accs. acc is cytoplasmic and appears to be distributed throughout t ... | 2011 | 21306439 |
| saccharomyces cerevisiae as a model organism: a comparative study. | model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. such organisms should be representative of the living beings for which they are to serve as proxy. however, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking. | 2011 | 21311596 |
| rho gtpase cdc42 is a direct interacting partner of adenomatous polyposis coli protein and can alter its cellular localization. | adenomatous polyposis coli (apc) is a tumor suppressor gene product involved in colon cancer. apc is a large multidomain molecule of 2843 amino acid residues and connects cell-cell adhesion, the f-actin/microtubule cytoskeleton and the nucleus. here we show that cdc42 interacts directly with the first three armadillo repeats of apc by yeast two-hybrid screens. we confirm the cdc42-apc interaction using pulldown assays in vitro and fret assays in vivo. interestingly, cdc42 interacts with apc at l ... | 2011 | 21311754 |
| synthesis and biological activity of splitomicin analogs targeted at human nad(+)-dependent histone deacetylases (sirtuins). | small molecules interfering with posttranslational modification of histones are of interest as tools to study epigenetic regulation of gene transcription. specifically, drugs that interfere with histone deacetylation could be useful to induce differentiation, growth arrest as well as apoptotic cell death in tumor cells. one class of histone deacetylases is known as sirtuins some of which (saccharomyces cerevisiae sir2) are for example inhibited by the lactone splitomicin leading to telomeric sil ... | 2011 | 21315612 |
| the essential role of fkbp38 in regulating phosphatase of regenerating liver 3 (prl-3) protein stability. | the phosphatase of regenerating liver-3 (prl-3) is a member of protein tyrosine phosphatases and whose deregulation is implicated in tumorigenesis and metastasis of many cancers. however, the underlying mechanism by which prl-3 is regulated is not known. in this study, we identified the peptidyl prolyl cis/trans isomerase fk506-binding protein 38 (fkbp38) as an interacting protein of prl-3 using a yeast two-hybrid system. fkbp38 specifically binds to prl-3 in vivo, and that the n-terminal region ... | 2011 | 21320469 |
| detecting protein-protein interactions in vesicular stomatitis virus using a cytoplasmic yeast two hybrid system. | protein-protein interactions play an important role in many virus-encoded functions and in virus-host interactions. while a "classical" yeast two-hybrid system (y2h) is one of the most common techniques to detect such interactions, it has a number of limitations, including a requirement for the proteins of interest to be relocated to the nucleus. modified y2h, such as the sos recruitment system (srs), which detect interactions occurring in the cytoplasm rather than the nucleus, allow proteins fr ... | 2011 | 21320532 |
| xenopus hjurp and condensin ii are required for cenp-a assembly. | centromeric protein a (cenp-a) is the epigenetic mark of centromeres. cenp-a replenishment is necessary in each cell cycle to compensate for the dilution associated to dna replication, but how this is achieved mechanistically is largely unknown. we have developed an assay using xenopus egg extracts that can recapitulate the spatial and temporal specificity of cenp-a deposition observed in human cells, providing us with a robust in vitro system amenable to molecular dissection. here we show that ... | 2011 | 21321101 |
| a generic system for the expression and purification of soluble and stable influenza neuraminidase. | the influenza surface glycoprotein neuraminidase (na) is essential for the efficient spread of the virus. antiviral drugs such as tamiflu (oseltamivir) and relenza (zanamivir) that inhibit na enzyme activity have been shown to be effective in the treatment of influenza infections. the recent 'swine flu' pandemic and world-wide emergence of tamiflu-resistant seasonal human influenza a(h1n1) h(274)y have highlighted the need for the ongoing development of new anti-virals, efficient production of v ... | 2011 | 21326879 |
| mutations causing greenberg dysplasia but not pelger anomaly uncouple enzymatic from structural functions of a nuclear membrane protein. | the lamin b receptor (lbr) is an inner nuclear membrane protein with a structural function interacting with chromatin and lamins, and an enzymatic function as a sterol reductase. heterozygous lbr mutations cause nuclear hyposegmentation in neutrophils (pelger anomaly), while homozygous mutations cause prenatal death with skeletal defects and abnormal sterol metabolism (greenberg dysplasia). it has remained unclear whether the lethality in greenberg dysplasia is due to cholesterol defects or alte ... | 2010 | 21327084 |
| interaction between nucleosome assembly protein 1-like family members. | mammals possess five nucleosome assembly protein 1-like (nap1l) proteins, with three of them being expressed exclusively in the nervous system. the biological importance of the neuron-specific nap1l2 protein is demonstrated by the neural tube defects occurring during the embryonic development of nap1l2 mutant mice, which are associated with an overproliferation of neural stem cells and decreased neuronal differentiation. nap1l2 controls the expression of its target genes, such as the cell cycle ... | 2011 | 21333655 |
| distinct regulation of p53-mediated apoptosis by protein kinase ca, d, e and ?: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms. | the role of individual protein kinase c (pkc) isoforms in the regulation of p53-mediated apoptosis is still uncertain. using yeast cells co-expressing the human wild-type p53 and a single mammalian pkca, d, e or ?, we showed a differential regulation of p53-mediated apoptosis by these pkc isoforms. whereas pkca and ? had no effect on p53 activity, pkcd and e stimulated a p53-mediated mitochondria-dependent apoptosis. moreover, using pifithrin-a and -µ, selective inhibitors of p53 transcriptional ... | 2011 | 21338602 |
| development of chromanes as novel inhibitors of the uncoupling proteins. | the uncoupling proteins (ucps) are mitochondrial carriers that modulate the energetic efficiency and, as a result, can lower superoxide levels. here, we describe the discovery of a small-molecule inhibitor of the ucps. screening of potential ucp1 regulators led to the identification of chromane derivatives that inhibit its proton conductance. members of the ucp family can act as a defense against oxidative stress and, thus, ucp2 plays a protective role in tumor cells. high ucp2 levels have been ... | 2011 | 21338923 |
| xenotransplantation of mitochondrial electron transfer enzyme, ndi1, in myocardial reperfusion injury. | a significant consequence of ischemia/reperfusion (i/r) is mitochondrial respiratory dysfunction, leading to energetic deficits and cellular toxicity from reactive oxygen species (ros). mammalian complex i, a nadh-quinone oxidoreductase enzyme, is a multiple subunit enzyme that oxidizes nadh and pumps protons across the inner membrane. damage to complex i leads to superoxide production which further damages complex i as well as other proteins, lipids and mtdna. the yeast, s. cerevisiae, expresse ... | 2011 | 21339825 |
| membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme a reductase. | the endoplasmic reticulum (er)-associated degradation (erad) pathway in the yeast saccharomyces cerevisiae is mediated by two membrane-bound ubiquitin ligases, doa10 and hrd1. these enzymes are found in distinct multiprotein complexes that allow them to recognize and target a variety of substrates for proteasomal degradation. although multiprotein complexes containing mammalian erad ubiquitin ligases likely exist, they have yet to be identified and characterized in detail. here, we identify two ... | 2011 | 21343306 |
| hzwint-1 bridges the inner and outer kinetochore: identification of the kinetochore localization domain and the hzw10-interaction domain. | accurate chromosome segregation in mitosis is required to maintain genetic stability. hzwint-1 [human zw10 (zeste white 10)-interacting protein 1] is a kinetochore protein known to interact with the kinetochore checkpoint protein hzw10. hzw10, along with its partners rod (roughdeal) and hzwilch, form a complex which recruits dynein-dynactin and mad1-mad2 complexes to the kinetochore and are essential components of the mitotic checkpoint. hzwint-1 localizes to the kinetochore in prophase, before ... | 2011 | 21345172 |
| pharmacokinetic-pharmacodynamic modeling of the inhibitory effects of naproxen on the time-courses of inflammatory pain, fever, and the ex vivo synthesis of txb2 and pge2 in rats. | to quantify and compare the time-course and potency of the analgesic and antipyretic effects of naproxen in conjunction with the inhibition of pge(2) and txb(2). | 2011 | 21347567 |
| phosphate-responsive signaling pathway is a novel component of nad+ metabolism in saccharomyces cerevisiae. | nicotinamide adenine dinucleotide (nad(+)) is an essential cofactor involved in various cellular biochemical reactions. to date the signaling pathways that regulate nad(+) metabolism remain unclear due to the dynamic nature and complexity of the nad(+) metabolic pathways and the difficulty of determining the levels of the interconvertible pyridine nucleotides. nicotinamide riboside (nmr) is a key pyridine metabolite that is excreted and re-assimilated by yeast and plays important roles in the ma ... | 2011 | 21349851 |
| [development of a yeast two-hybrid screen for selection of a/h1n1 influenza ns1 non-structural protein and human cpsf30 protein interaction inhibitors]. | influenza a/h1n1 virus-encoded nonstructural, or ns1, protein inhibits the 3'-end processing of cellular pre-mrnas by binding the cellular protein: the 30-kda subunit of cpsf (cleavage and polyadenylation specificity factor, cpsf30). cpsf30 binding site of the ns1 protein is a potential target for the development of drugs against influenza a/h1n1 virus. a yeast two-hybrid screening system was constructed and used for screening chinese medicines that inhibit the interaction of the a/h1n1 flu ns1 ... | 2010 | 21351518 |
| transcriptional and cellular responses to defective mitochondrial proteolysis in fission yeast. | lon and m-aaa are the principal, regulated proteases required for protein maturation and turnover in the mitochondrial matrix of diverse species. to understand their roles in fission yeast (schizosaccharomyces pombe) mitochondria, we generated deletion strains lacking lon and m-aaa, individually (?lon1 and ?m-aaa) or together, ?lon1?m-aaa (?/?). all three strains were viable but incapable of respiratory growth on a non-fermentable carbon source due to mitochondrial dysfunction. confocal and elec ... | 2011 | 21354177 |
| haploinsufficiency and the sex chromosomes from yeasts to humans. | haploinsufficient (hi) genes are those for which a reduction in copy number in a diploid from two to one results in significantly reduced fitness. haploinsufficiency is increasingly implicated in human disease, and so predicting this phenotype could provide insights into the genetic mechanisms behind many human diseases, including some cancers. | 2011 | 21356089 |
| identification and characterization of the mitochondrial rna polymerase and transcription factor in the fission yeast schizosaccharomyces pombe. | we have characterized the mitochondrial transcription factor (mtf1) and rna polymerase (rpo41) of schizosaccharomyces pombe. deletion mutants show mtf1 or rpo41 to be essential for cell growth, cell morphology and mitochondrial membrane potential. overexpression of mtf1 and rpo41 can induce mitochondrial transcription. mtf1 and rpo41 can bind and transcribe mitochondrial promoters in vitro and the initiating nucleotides were the same in vivo and in vitro. mtf1 is required for efficient transcrip ... | 2011 | 21357609 |
| elongator protein 3b negatively regulates ribosomal dna transcription in african trypanosomes. | eukaryotic cells limit ribosomal dna (rdna) transcription by rna polymerase i (rnap-i) to maintain genome integrity. african trypanosomes present an excellent model for studies on rnap-i regulation because they possess a bifunctional rnap-i and because rnap-ii transcription appears unregulated. since elp3, the catalytic component of elongator, controls rnap-ii transcription in yeast and human cells, we predicted a role for a trypanosome elp3-related protein, elp3a or elp3b, in rnap-i regulation. ... | 2011 | 21357738 |
| mutations in origin recognition complex gene orc4 cause meier-gorlin syndrome. | meier-gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae. using marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes, we identified three different mutations in the gene encoding orc4, a component of the eukaryotic origin recognition complex, in five individuals with meier-gorlin syndrome. in t ... | 2011 | 21358631 |