Publications

intrachromosomal gene amplification triggered by hairpin-capped breaks requires homologous recombination and is independent of nonhomologous end-joining.	gene amplification is one of the major mechanisms of acquisition of drug resistance and activation of oncogenes in tumors. in mammalian cells, amplified chromosomal regions are manifested cytogenetically as extrachromosomal double minutes (dms) and chromosomal homogeneously staining regions (hsrs). we recently demonstrated using yeast model system that hairpin-capped double strand breaks (dsbs) generated at the location of human alu-quasipalindromes can trigger both types of gene amplification. ...	2007	17671429
nbs1 is involved in dna repair and plays a synergistic role with atm in mediating meiotic homologous recombination in plants.	the ability of plants to repair dna double-strand breaks (dsbs) is essential for growth and fertility. the arabidopsis dsb repair proteins atrad50 and atmre11 form part of an evolutionarily conserved complex that, in saccharomyces cerevisiae and mammals, includes a third component termed xrs2 and nbs1, respectively. the mrn complex (mrx in yeast) has a direct role in dsb repair and is also required for dna damage signaling and checkpoint activation in a pathway mediated by the protein kinase atm ...	2007	17672843
a predicted interactome for arabidopsis.	the complex cellular functions of an organism frequently rely on physical interactions between proteins. a map of all protein-protein interactions, an interactome, is thus an invaluable tool. we present an interactome for arabidopsis (arabidopsis thaliana) predicted from interacting orthologs in yeast (saccharomyces cerevisiae), nematode worm (caenorhabditis elegans), fruitfly (drosophila melanogaster), and human (homo sapiens). as an internal quality control, a confidence value was generated ba ...	2007	17675552
proteomic parsimony through bipartite graph analysis improves accuracy and transparency.	assembling peptides identified from lc-ms/ms spectra into a list of proteins is a critical step in analyzing shotgun proteomics data. as one peptide sequence can be mapped to multiple proteins in a database, naïve protein assembly can substantially overstate the number of proteins found in samples. we model the peptide-protein relationships in a bipartite graph and use efficient graph algorithms to identify protein clusters with shared peptides and to derive the minimal list of proteins. we test ...	2007	17676885
orthology and functional conservation in eukaryotes.	in recent years, it has become clear that all of the organisms on the earth are related to each other in ways that can be documented by molecular sequence comparison. in this review, we focus on the evolutionary relationships among the proteins of the eukaryotes, especially those that allow inference of function from one species to another. data and illustrations are derived from specific comparison of eight species: homo sapiens, mus musculus, arabidopsis thaliana, caenorhabditis elegans, danio ...	2007	17678444
regulation of human cytidine triphosphate synthetase 1 by glycogen synthase kinase 3.	cytidine triphosphate synthetase (ctps) catalyzes the rate-limiting step in the de novo synthesis of ctp, and both the yeast and human enzymes have been reported to be regulated by protein kinase a or protein kinase c phosphorylation. here, we provide evidence that stimulation or inhibition of protein kinase a and protein kinase c does not alter the phosphorylation of endogenous human ctps1 in human embryonic kidney 293 cells under the conditions tested. unexpectedly, we found that low serum con ...	2007	17681942
htra2 regulates beta-amyloid precursor protein (app) metabolism through endoplasmic reticulum-associated degradation.	alzheimer disease-associated beta-amyloid peptide is generated from its precursor protein app. by using the yeast two-hybrid assay, here we identified htra2/omi, a stress-responsive chaperone-protease as a protein binding to the n-terminal cysteinerich region of app. htra2 coimmunoprecipitates exclusively with immature app from cell lysates as well as mouse brain extracts and degrades app in vitro. a subpopulation of htra2 localizes to the cytosolic side of the endoplasmic reticulum (er) membran ...	2007	17684015
estrogen-like effect of a cimicifuga racemosa extract sub-fraction as assessed by in vivo, ex vivo and in vitro assays.	black cohosh (cimicifuga racemosa) is used in the treatment of painful menstruation and menopausal symptoms. data about the nature of the active compounds and mechanism(s) of action are still controversial, chiefly with respect to its estrogenic activity. this work aimed to assess the possible estrogenic activity of a commercial dry hydro-alcoholic extract of c. racemosa and its hydrophilic and lipophilic sub-fractions on in vivo, ex vivo, and in vitro assays. in a yeast estrogen screen, only th ...	2007	17689956
activation of estrogen receptor-beta by a special extract of rheum rhaponticum (err 731), its aglycones and structurally related compounds.	the special extract err 731 from the roots of rheum rhaponticum is the major constituent of phytoestrol n which is used for the treatment of climacteric symptoms in menopausal women. however, the molecular mode of action of err 731 was unknown. for the first time, err 731 and its aglycones trans-rhapontigenin and desoxyrhapontigenin were investigated with regard to the activation of the estrogen receptor-alpha or estrogen receptor-beta (eralpha, erbeta). the related hydroxystilbenes cis-rhaponti ...	2007	17692514
an investigation into 53bp1 complex formation.	loss of the control over cellular proliferation can lead to cell death or result in the abnormal proliferation characteristic of the cancerous state. among the controls used to achieve normal cellular proliferation is the dna damage checkpoint pathway that monitors genome integrity (hartwell and kastan 1994). 53bp1 was identified as a protein that interacts with the dna-binding core domain of the tumor suppressor p53. the p53-binding region of 53bp1 maps to the c-terminal brct domains which are ...	2007	17695720
a screen for suppressors of gross chromosomal rearrangements identifies a conserved role for plp in preventing dna lesions.	genome instability is a hallmark of cancer cells. one class of genome aberrations prevalent in tumor cells is termed gross chromosomal rearrangements (gcrs). gcrs comprise chromosome translocations, amplifications, inversions, deletion of whole chromosome arms, and interstitial deletions. here, we report the results of a genome-wide screen in saccharomyces cerevisiae aimed at identifying novel suppressors of gcr formation. the most potent novel gcr suppressor identified is bud16, the gene coding ...	2007	17696614
a role for yeast and human translesion synthesis dna polymerases in promoting replication through 3-methyl adenine.	3-methyl adenine (3mea), a minor-groove dna lesion, presents a strong block to synthesis by replicative dna polymerases (pols). to elucidate the means by which replication through this dna lesion is mediated in eukaryotic cells, here we carry out genetic studies in the yeast saccharomyces cerevisiae treated with the alkylating agent methyl methanesulfonate. from the studies presented here, we infer that replication through the 3mea lesion in yeast cells can be mediated by the action of three rad ...	2007	17698580
rescuing yeast mutants with human genes.	the fission yeast schizosaccharomyces pombe and the budding yeast saccharomyces cerevisiae have, in addition to being extensively studied themselves, both been utilized for the last quarter century as experimental systems for the isolation of genes from other organisms. mutations conferring growth defects in either of the two yeast strains have frequently been complemented by expression of cdna libraries from heterologous species, often human. many successful experiments have utilized available ...	2007	17698857
increasing selenium concentration in milk: effects of amount of selenium from yeast and cereal grain supplements.	two experiments were conducted to establish responses in milk se concentrations in grazing dairy cows to different amounts of dietary se yeast, and to determine the effects of the se concentration of the basal diet. the hypothesis tested was that the response in milk, blood, and tissue se concentrations to supplemental se would not be affected by whether the se was from the basal diet or from se yeast. in addition, by conducting a similar experiment in either early (spring; experiment 1) or late ...	2007	17699029
recruitment of factors linking transcription and processing of pre-rrna to nor chromatin is ubf-dependent and occurs independent of transcription in human cells.	efficient ribosome biogenesis requires coordination of a highly complex series of events. early events include pre-rna transcription, processing, and modification. analysis in yeast has demonstrated that t-utps, components of the u3 snorna-containing pre-rrna processing complex, are required for efficient transcription of ribosomal genes (rdna) by rna polymerase i (pol i). here, we characterize human t-utps and establish that their ability to link transcription and pre-rrna processing is evoluti ...	2007	17699751
mutational analysis of the tre2 oncogene encoding an inactive rabgap.	the tre2 oncoprotein is structurally related to the rabgap (gtpase-activating protein) family. however, tre2 seems enzymatically inactive. two regions are important for its lack of gap activity. first, the tbc domain, forming the catalytically active domain of rabgaps, is non-functional in the oncoprotein. also involved in tre2 inactivity is the 93-aa region flanking the tbc domain on the c-terminal side. in order to identify the residues responsible for non-functionality, we performed hydrophob ...	2007	17701273
dna damage leaves its mark on chromatin.	dna organization into chromatin has a major influence on the cellular response to dna damage. recent studies in various systems ranging from yeast to human cells stress the importance of chromatin not simply as a barrier to dna repair processes but also as an active contributor to the dna damage response. indeed, modulations of chromatin organization involving various degrees of rearrangements, such as histone modifications and even nucleosome displacement, can promote efficient repair and also ...	2007	17703111
synthesis, transportability and hypoxiaselective binding of 1-beta-d-(5-deoxy-5-fluororibofuranosyl)-2-nitroimidazole (beta-5-fazr), a configurational isomer of the clinical hypoxia marker, faza.	cellular uptake of most azomycin-based radiosensitizers depends on perfusion and diffusion, rather than on active transport. in medical imaging using radioisotopically labeled azomycin nucleosides, image contrast depends on rapid diffusion from normoxic tissues and rapid renal clearance from the central compartment. [18f]faza [1-alpha-d-(5-deoxy-18f]fluoroarabinofuranosyl)-2-nitroimidazole], an azomycin nucleoside currently under clinical evaluation as a marker of tissue hypoxia in medical cente ...	2007	17706182
high-throughput fluorescent-based optimization of eukaryotic membrane protein overexpression and purification in saccharomyces cerevisiae.	eukaryotic membrane proteins are often difficult to produce in large quantities, which is a significant obstacle for further structural and biochemical investigation. based on the analysis of 43 eukaryotic membrane proteins, we present a cost-effective high-throughput approach for rapidly screening membrane proteins that can be overproduced to levels of >1 mg per liter in saccharomyces cerevisiae. we find that 70% of the well expressed membrane proteins tested in this system are stable, targeted ...	2007	17709746
phosphorylation and activation of the atypical kinase p53-related protein kinase (prpk) by akt/pkb.	p53-related protein kinase (prpk), the human homologue of yeast bud32, belonging to a small subfamily of atypical protein kinases, is inactive unless it is previously incubated with cell lysates. here we show that such an activation of prpk is mediated by another kinase, akt/pkb, which phosphorylates prpk at ser250. we show that recombinant prpk is phosphorylated in vitro by akt and its phospho-form is recognized by a ser250-phospho-specific antibody; that cell co-transfection with akt along wit ...	2007	17712528
regulation of repp86 stability by human siah2.	human repp86 is a nuclear protein that is expressed in a tightly limited period of time during the cell cycle and plays an essential role in its progression. manipulation of repp86 expression by reduction of endogenous repp86 or overexpression of exogenous repp86 results in cell cycle arrest. we found that repp86 interacts with human siah2, which is a known mediator for proteasomal degradation. siah2 failed to interact with repp86 lacking the first 67 n-terminal amino acids. overexpression of si ...	2007	17716627
atp-dependent assembly of the human origin recognition complex.	the origin recognition complex (orc) was initially discovered in budding yeast extracts as a protein complex that binds with high affinity to autonomously replicating sequences in an atp-dependent manner. we have cloned and expressed the human homologs of the orc subunits as recombinant proteins. in contrast to other eukaryotic initiators examined thus far, assembly of human orc in vitro is dependent on atp binding. mutations in the atp-binding sites of orc4 or orc5 impair complex assembly, wher ...	2007	17716973
the par-1/mark family of protein kinases: from polarity to metabolism.	the par-1 protein kinases are conserved from yeast to man and belong to a subfamily of kinases that includes the energy sensor and metabolic regulator, ampk. par-1 is regulated by lkb1 and atypical pkc and has been shown in multiple organisms and cell types to be critical for regulation of cellular polarity. recent studies using knockout mice have revealed several surprising physiological functions for par-1b/mark2/emk1. our recent study shows that par-1b regulates metabolic rate, adiposity and ...	2007	17721078
antitumour drugs impede dna uncoiling by topoisomerase i.	increasing the ability of chemotherapeutic drugs to kill cancer cells is often hampered by a limited understanding of their mechanism of action. camptothecins, such as topotecan, induce cell death by poisoning dna topoisomerase i, an enzyme capable of removing dna supercoils. topotecan is thought to stabilize a covalent topoisomerase-dna complex, rendering it an obstacle to dna replication forks. here we use single-molecule nanomanipulation to monitor the dynamics of human topoisomerase i in the ...	2007	17589503
cloning and characterization of dppl1 and dppl2, representatives of a novel type of mammalian phosphatidate phosphatase.	phosphatidate phosphatase (pap) enzymes are classified as either mg(2+)-dependent (pap1) or mg(2+)-independent (pap2) with respect to their mg(2+) cofactor requirement for catalytic activity. sensitivity to the thioreactive compound n-ethylmaleimide (nem) has also been used to differentiate pap1 (nem-sensitive) from pap2 (nem-insensitive) activity in mammalian cells. we report here the cloning and initial characterization of dppl1 and dppl2, representatives of a novel type of mammalian phosphati ...	2007	17590538
high-level expression in saccharomyces cerevisiae enables isolation and spectroscopic characterization of functional human adenosine a2a receptor.	the g-protein coupled receptors (gpcrs) are a class of membrane proteins that trigger cellular responses to external stimuli, and are believed to be targets for nearly half of all pharmaceutical drugs on the market. however, little is known regarding their folding and cellular interactions, as well as what factors are crucial for their activity. further structural characterization of gpcrs has largely been complicated by problems with expression, purification, and preservation of activity in vit ...	2007	17591446
[the nucleolus as a regulator of cellular senescence].	the nucleolus has been considered originally only as the site for the ribosome synthesis, but now it is well known that it represents a dynamic nuclear structure involved in important cellular processes. several evidences have demonstrated that the nucleolus regulates the cellular senescence. specific mutations on the dnas codifying for nucleolar proteins induced premature senescence from yeast to human. the failure to repress the genes transcription codifying for damaged rrna, and the mutations ...	2007	17593607
h2o2 accelerates cellular senescence by accumulation of acetylated p53 via decrease in the function of sirt1 by nad+ depletion.	it has been reported that p53 acetylation, which promotes cellular senescence, can be regulated by the nad(+)-dependent deacetylase sirt1, the human homolog of yeast sir2, a protein that modulates lifespan. to clarify the role of sirt1 in cellular senescence induced by oxidative stress, we treated normal human diploid fibroblast tig-3 cells with h(2)o(2) and examined dna cleavage, depletion of intracellular nad(+), expression of p21, sirt1, and acetylated p53, cell cycle arrest, and senescence-a ...	2007	17595514
dual e1 activation systems for ubiquitin differentially regulate e2 enzyme charging.	modification of proteins with ubiquitin or ubiquitin-like proteins (ubls) by means of an e1-e2-e3 cascade controls many signalling networks. ubiquitin conjugation involves adenylation and thioesterification of the carboxy-terminal carboxylate of ubiquitin by the e1-activating enzyme ube1 (uba1 in yeast), followed by ubiquitin transfer to an e2-conjugating enzyme through a transthiolation reaction. charged e2s function with e3s to ubiquitinate substrates. it is currently thought that ube1/uba1 is ...	2007	17597759
cgmp-dependent protein kinase i interacts with trim39r, a novel rpp21 domain-containing trim protein.	nitric oxide modulates vascular smooth muscle cell (smc) cytoskeletal kinetics and phenotype, in part, by stimulating cgmp-dependent protein kinase i (pkgi). to identify molecular targets of pkgi, an interaction trap screen in yeast was performed using a cdna encoding the catalytic region of pkgi and a human lung cdna library. we identified a cdna that encodes a putative pkgi-interactor that is a novel variant of trim39, a member of the really interesting new gene (ring) finger family of protein ...	2007	17601797
reconstructing the evolution of the mitochondrial ribosomal proteome.	for production of proteins that are encoded by the mitochondrial genome, mitochondria rely on their own mitochondrial translation system, with the mitoribosome as its central component. using extensive homology searches, we have reconstructed the evolutionary history of the mitoribosomal proteome that is encoded by a diverse subset of eukaryotic genomes, revealing an ancestral ribosome of alpha-proteobacterial descent that more than doubled its protein content in most eukaryotic lineages. we obs ...	2007	17604309
cornichon regulates transport and secretion of tgfalpha-related proteins in metazoan cells.	cornichon proteins are structurally related transmembrane proteins that have been studied in and drosophila and yeast. in drosophila, cornichon (cni) is involved in embryo polarization by the tgfalpha-related gurken. in yeast, the cni-related erv14 is required for axial budding. a cargo receptor function has been proposed for erv14 and cni. four mammalian cni-like sequences have been identified. we carried out parallel functional analyses of the human cni ortholog cnih and drosophila cni in the ...	2007	17607000
live cell fret microscopy: homo- and heterodimerization of two human peroxisomal abc transporters, the adrenoleukodystrophy protein (aldp, abcd1) and pmp70 (abcd3).	the adrenoleukodystrophy protein (aldp) and the 70-kda peroxisomal membrane protein (pmp70) are half-atp-binding cassette (abc) transporters in the mammalian peroxisome membrane. mutations in the gene encoding aldp result in a devastating neurodegenerative disorder, x-linked adrenoleukodystrophy (x-ald) that is associated with elevated levels of very long chain fatty acids because of impaired peroxisomal beta-oxidation. the interactions of peroxisomal abc transporters, their role in the peroxiso ...	2007	17609205
deletion of the high-affinity camp phosphodiesterase encoded by pde2 affects stress responses and virulence in candida albicans.	previously, we have shown that pde2 is required for hyphal development and cell wall integrity in candida albicans. in the present study, we have investigated the effects of its deletion by genome-wide transcriptome profiling. changes in expression levels of genes involved in metabolism, transcription, protein and nucleic acids synthesis, as well as stress responses, cell wall and membrane biogenesis, adherence and virulence have been observed. by comparing these changes with previously reported ...	2007	17614954
multiple conserved domains of the nucleoporin nup124p and its orthologs nup1p and nup153 are critical for nuclear import and activity of the fission yeast tf1 retrotransposon.	the nucleoporin nup124p is a host protein required for the nuclear import of both, retrotransposon tf1-gag as well as the retroviral hiv-1 vpr in fission yeast. the human nucleoporin nup153 and the saccharomyces cerevisiae nup1p were identified as orthologs of nup124p. in this study, we show that all three nucleoporins share a large fg/fxfg-repeat domain and a c-terminal peptide sequence, grkixxxxxrrkx, that are absolutely essential for tf1 retrotransposition. though the fxfg domain was essentia ...	2007	17615301
increase of calnexin gene dosage boosts the secretion of heterologous proteins by hansenula polymorpha.	the type i membrane protein calnexin is a conserved key component of the quality control mechanism in the endoplasmic reticulum. it functions as a molecular chaperone that monitors the folding state of nascent polypeptides entering the endoplasmic reticulum. calnexin also behaves as a lectin, as its chaperoning activity involves binding of oligosaccharide moieties present on newly imported glycoproteins. we isolated the calnexin gene (hpcne1) from the methylotrophic yeast hansenula polymorpha, a ...	2007	17617219
the cora family: structure and function revisited.	the cora family is a group of ion transporters that mediate transport of divalent metal ions across biological membranes. metal ions are essential elements in most cellular processes and hence the concentrations of ions in cells and organelles must be kept at appropriate levels. impairment of these systems is implied in a number of pathological conditions. cora proteins are abundant among the prokaryotic organisms but homologues are present in both human and yeast. the activity of cora proteins ...	2007	17619822
eclipsed distribution: a phenomenon of dual targeting of protein and its significance.	one of the surprises from genome sequencing projects is the apparently small number of predicted genes in different eukaryotic cells, particularly human. one possible reason for this 'shortage' of genes is multiple distribution of proteins; a single protein is targeted to more than one subcellular compartment and consequently participates in different biochemical pathways and might have completely different functions. indeed, in recent years, there have been reports on proteins that were found t ...	2007	17621655
molecular and structural transactions at human dna replication origins.	the dna replication origins of metazoan genomes are the sites of complex sequence-specific protein-dna interactions determining their precise cycle of activation and deactivation, once only along each cell cycle. some of the involved proteins have been identified (and particularly the essential six-protein origin recognition complex, orc) thanks to their homology with the proteins identified in yeast. whereas in the latter organism orc has a specific affinity for an origin consensus, metazoan (a ...	2007	17622799
chromatin remodeling proteins interact with pericentrin to regulate centrosome integrity.	pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. in a yeast two-hybrid screen with pericentrin we identified chromodomain helicase dna-binding protein 4 (chd4/mi2beta). chd4 is part of the multiprotein nucleosome remodeling deacetylase (nurd) complex. we show that many nurd components interacted with pericentrin by coimmunoprecipitation and that they localized to centrosomes and midbodies. overexpression of the pericentrin-binding ...	2007	17626165
recognition of polyadenosine rna by zinc finger proteins.	messenger rna transcripts are coated from cap to tail with a dynamic combination of rna binding proteins that process, package, and ultimately regulate the fate of mature transcripts. one class of rna binding proteins essential for multiple aspects of mrna metabolism consists of the poly(a) binding proteins. previous studies have concentrated on the canonical rna recognition motif-containing poly(a) binding proteins as the sole family of poly(a)-specific rna binding proteins. in this study, we p ...	2007	17630287
[identification of binding proteins to the pdz domain of erbin].	to identify the binding proteins to pdz domain of erbin.	2007	17633453
genomic signal processing: from matrix algebra to genetic networks.	dna microarrays make it possible, for the first time, to record the complete genomic signals that guide the progression of cellular processes. future discovery in biology and medicine will come from the mathematical modeling of these data, which hold the key to fundamental understanding of life on the molecular level, as well as answers to questions regarding diagnosis, treatment, and drug development. this chapter reviews the first data-driven models that were created from these genome-scale da ...	2007	17634608
clinical, structural and functional implications of mutations and polymorphisms in human nadph p450 oxidoreductase.	cytochrome p450 proteins are involved in metabolism of drugs and xenobiotics. in the endoplasmic reticulum a single nicotinamide adenine dinucleotide phosphate (nadph) p450 oxidoreductase (por) supplies electrons to all microsomal p450s for catalytic activity. por is a flavoprotein that contains both flavin mononucleotide and flavin adenine dinucleotide as cofactors and uses nadph as the source of electrons. we have recently reported a number of por mutations in the patients with disordered ster ...	2007	17635179
the camp pathway is important for controlling the morphological switch to the pathogenic yeast form of paracoccidioides brasiliensis.	paracoccidioides brasiliensis is a human pathogenic fungus that switches from a saprobic mycelium to a pathogenic yeast. consistent with the morphological transition being regulated by the camp-signalling pathway, there is an increase in cellular camp levels both transiently at the onset (< 24 h) and progressively in the later stages (> 120 h) of the transition to the yeast form, and this transition can be modulated by exogenous camp. we have cloned the cyr1 gene encoding adenylate cyclase (ac) ...	2007	17635191
uxt interacts with the transcriptional repressor protein evi1 and suppresses cell transformation.	the evi1 transcriptional repressor is critical to the normal development of a variety of tissues and participates in the progression of acute myeloid leukaemias. the repressor domain (rp) was used to screen an adult human kidney yeast two-hybrid library and a novel binding partner designated ubiquitously expressed transcript (uxt) was isolated. enforced expression of uxt in evi1-expressing rat1 fibroblasts suppresses cell transformation and uxt may therefore be a negative regulator of evi1 biolo ...	2007	17635584
monoubiquitylation of h2a.z distinguishes its association with euchromatin or facultative heterochromatin.	h2a.z is a histone h2a variant that is essential for viability in organisms such as tetrahymena thermophila, drosophila melanogaster, and mice. in saccharomyces cerevisiae, loss of h2a.z is tolerated, but proper regulation of gene expression is affected. genetics and genome-wide localization studies show that yeast h2a.z physically localizes to the promoters of genes and functions in part to protect active genes in euchromatin from being silenced by heterochromatin spreading. to date, the functi ...	2007	17636032
heat shock protein 70 interacts with aquaporin-2 and regulates its trafficking.	the trafficking of aquaporin-2 (aqp2) involves multiple complex pathways, including regulated, camp-, and cgmp-mediated pathways, as well as a constitutive recycling pathway. although several accessory proteins have been indirectly implicated in aqp2 recycling, the direct protein-protein interactions that regulate this process remain largely unknown. using yeast two-hybrid screening of a human kidney cdna library, we have identified the 70-kda heat shock proteins as aqp2-interacting proteins. in ...	2007	17636261
interactions between conserved domains within homodimers in the big1, big2, and gbf1 arf guanine nucleotide exchange factors.	guanine nucleotide exchange factors carrying a sec7 domain (arfgefs) activate the small gtp-binding protein arf, a major regulator of membrane remodeling and protein trafficking in eukaryotic cells. only two of the seven subfamilies of arfgefs (gbf and big) are found in all eukaryotes. in addition to the sec7 domain, which catalyzes gdp/gtp exchange on arf, the gbf and big arfgefs have five common homology domains. very little is known about the functions of these noncatalytic domains, but it is ...	2007	17640864
bcl3 acts as a negative regulator of transcription from the human t-cell leukemia virus type 1 long terminal repeat through interactions with torc3.	by associating with cyclic amp-responsive element-binding protein (creb), the human t-cell leukemia virus type 1 (htlv-1) tax protein activates transcription from the htlv-1 long terminal repeat (ltr), which contains multiple cyclic amp-responsive elements. the transducers of regulated creb activity (torcs) were a recently identified family of creb co-activators that bind to creb to enhance cre-mediated transcription. torc3, a torc family protein, dramatically enhances tax-mediated transcription ...	2007	17644518
computational analysis of human protein interaction networks.	large amounts of human protein interaction data have been produced by experiments and prediction methods. however, the experimental coverage of the human interactome is still low in contrast to predicted data. to gain insight into the value of publicly available human protein network data, we compared predicted datasets, high-throughput results from yeast two-hybrid screens, and literature-curated protein-protein interactions. this evaluation is not only important for further methodological impr ...	2007	17647236
pttg is a secretory protein in human pituitary adenomas and in mouse pituitary tumor cell lines.	the pituitary tumor-transforming gene (pttg) is a homolog of yeast securin, which arrests the activation of separin to induce sister chromatid separation in the transition from metaphase to anaphase. pituitary tumor-transforming gene is also known to induce angiogenesis during pituitary tumorigenesis. it has not been clarified whether pttg functions as a cytoplasmic or a nuclear protein. our immunohistochemical study indicated that pttg is localized in the cytoplasm of pituitary tumor cells. in ...	2007	17652795
[microbiological identification and in vitro sensitivity of candida isolates from the oral cavity of hiv-positive individuals].	oropharyngeal candidiasis is the most common fungal infection among patients infected with the human immunodeficiency virus. it can be treated with either systemic or topical antifungal agents, which are indicated empirically on the basis of clinical data. the objective of this study was to determine the frequency of yeast in mouthwashes from hiv-positive patients, compare the results between patients presenting different states of immunodeficiency, and investigate the susceptibility profile of ...	2007	17653459
the copper, zinc superoxide dismutase gene of penicillium marneffei: cloning, characterization, and differential expression during phase transition and macrophage infection.	superoxide dismutase (sod) is an enzyme that converts superoxide radicals into hydrogen peroxide and oxygen molecules. sod has been shown to contribute to the virulence of many human-pathogenic fungi through its ability to neutralize toxic levels of reactive oxygen species generated by the host. sod has also been speculated to be important in the pathogenesis of fungal infections, but the role of this enzyme has not been rigorously investigated. in this report, we isolated and characterized the ...	2007	17654267
identification and characterization of a novel protein isoc2 that interacts with p16ink4a.	p16(ink4a) is a multiple tumor suppressor, playing an important role in proliferation and tumorigenesis. to screen the p16(ink4a)-associated proteins, we performed a yeast two-hybrid assay and identified a novel protein isochorismatase domain containing 2 (isoc2). isoc2 conserves in different species, and encodes 205 and 210 amino acids in human and mouse, respectively. the expression of isoc2 in mouse is universal but predominantly in uterus, stomach, and urinary tract system. interaction betwe ...	2007	17658461
circular dichroism studies of extracellular domains of human nicotinic acetylcholine receptors provide an insight into their structure.	the extracellular domains (ecds) of human nicotinic acetylcholine receptors (nachrs) are of major pharmacological interest as drug targets in the autoimmune disease myasthenia gravis and in various neurological disorders. we have previously expressed and purified the human muscle alpha1-, beta1-, gamma- and epsilon-nachr-ecds, as well as the wild type and a mutant of neuronal alpha7-ecd, in yeast pichia pastoris. the far-uv circular dichroism (cd) studies of these ecds, presented here, revealed ...	2007	17659334
interrogating yeast surface-displayed human proteome to identify small molecule-binding proteins.	identifying proteins that interact with small molecules is often a challenging step in understanding cellular signaling pathways or molecular mechanisms of drug action. in this report, we describe the construction of libraries displaying human protein fragments on the surface of yeast cells and demonstrate the utility of these libraries for the study of small molecule/protein interactions. the libraries were used to select protein fragments with affinity for the phosphatidylinositides phosphatid ...	2007	17660511
[na+/h+ antiporters from bacteria to human: ion transport mechanism and reguratory factors].		2007	17663161
evaluating polycyclic aromatic hydrocarbons using a yeast bioassay.	sixteen polycyclic aromatic hydrocarbons (pahs) were evaluated for the ability to activate aryl hydrocarbon (ah) receptor signaling in a yeast-based bioassay. individual pahs were classified as inactive or as weakly, moderately, or strongly active based on induction of human ah receptor signaling. indeno[1,2,3-cd]pyrene, chrysene, benzo[a]anthracene, benzo[a]pyrene, benzo[j]fluoranthene, and benzo[k]fluoranthene were the most potent activators of human ah receptor signaling. various mixtures of ...	2007	17665671
aryl hydrocarbon receptor ligand activity of polycyclic aromatic ketones and polycyclic aromatic quinones.	polycyclic aromatic ketones (paks) and polycyclic aromatic quinones (paqs) are oxygenated polycyclic aromatic hydrocarbons (pahs), and reports about the aryl hydrocarbon receptor (ahr) ligand activities of these compounds are few. in this study, activation of ahr by 41 polycyclic aromatic compounds (pacs), focusing especially on paks and paqs, was determined by measuring beta-galactosidase activity from a reporter plasmid in yeast engineered to express human ahr and the ahr nuclear translocator ...	2007	17665676
exploiting the yeast l-a viral capsid for the in vivo assembly of chimeric vlps as platform in vaccine development and foreign protein expression.	a novel expression system based on engineered variants of the yeast (saccharomyces cerevisiae) dsrna virus l-a was developed allowing the in vivo assembly of chimeric virus-like particles (vlps) as a unique platform for a wide range of applications. we show that polypeptides fused to the viral capsid protein gag self-assemble into isometric vlp chimeras carrying their cargo inside the capsid, thereby not only effectively preventing proteolytic degradation in the host cell cytosol, but also allow ...	2007	17476337
coiled coil structures and transcription: an analysis of the s. cerevisiae coilome.	the alpha-helical coiled coil is a simple but widespread motif that is an integral feature of many cellular structures. coiled coils allow monomeric building blocks to form complex assemblages that can serve as molecular motors and springs. previous parametrically delimited analyses of the distribution of coiled coils in the genomes of diverse organisms, including escherichia coli, saccharomyces cerevisiae, arabidopsis thaliana, caenorhabditis elegans and homo sapiens, have identified conserved ...	2007	17476531
a search engine to identify pathway genes from expression data on multiple organisms.	the completion of several genome projects showed that most genes have not yet been characterized, especially in multicellular organisms. although most genes have unknown functions, a large collection of data is available describing their transcriptional activities under many different experimental conditions. in many cases, the coregulatation of a set of genes across a set of conditions can be used to infer roles for genes of unknown function.	2007	17477880
foxg1, a member of the forkhead family, is a corepressor of the androgen receptor.	the androgen receptor (ar) is a ligand-dependent transcriptional regulator which belongs to the nuclear receptor superfamily. the basal transcriptional activity of the androgen receptor is regulated by interaction with coactivator or corepressor proteins. the exact mechanism whereby comodulators influence target gene transcription is only partially understood, especially for corepressors. whereas several coactivators are described for the ar, only a few corepressors are known. here, we describe ...	2007	17482455
human eosinophil-derived neurotoxin: involvement of a putative non-catalytic phosphate-binding subsite in its catalysis.	human eosinophil-derived neurotoxin (edn) or rnase 2, found in the non-core matrix of eosinophils is a ribonuclease belonging to the ribonuclease a superfamily. edn manifests a number of bioactions including neurotoxic and antiviral activities, which are dependent on its ribonuclease activity. the core of the catalytic site of edn contains various base and phosphate-binding subsites. unlike many members of the rnase a superfamily, edn contains an additional non-catalytic phosphate-binding subsit ...	2007	17483910
geminin organizes the molecular platform to balance cellular proliferation and differentiation.	geminin was originally identified as an inhibitor of replication initiation, but is now known to play multiple roles in several fundamental cellular processes including proliferation, differentiation, development and transcriptional regulation. recently, the functional properties of geminin have been further characterized by identifying geminin binding partners. to gain a broader molecular view of geminin's role in the control of cellular functions, we performed yeast two-hybrid screening. in th ...	2007	17485275
energy depletion protects candida albicans against antimicrobial peptides by rigidifying its cell membrane.	inhibitors of the energy metabolism, such as sodium azide and valinomycin, render yeast cells completely resistant against the killing action of a number of cationic antimicrobial peptides, including the salivary antimicrobial peptide histatin 5. in this study the histatin 5-mediated killing of the opportunistic yeast candida albicans was used as a model system to comprehensively investigate the molecular basis underlying this phenomenon. using confocal and electron microscopy it was demonstrate ...	2007	17485465
characterization of candida albicans infection of an in vitro oral epithelial model using confocal laser scanning microscopy.	oral candidosis presents as several distinct forms and one of these, chronic hyperplastic candidosis, is distinguished by penetration of the epithelium by candida. the aim of this study was to use confocal laser scanning microscopy to examine invasion of the oral epithelium by candida albicans from different oral conditions and to determine whether inherent strain differences exist that could relate to infection type. reverse transcription-polymerase chain reaction was also used to detect produc ...	2007	17488445
identification of a ligand for igg-fc derived from a soluble peptide library based on fusion proteins secreted by s. cerevisiae.	biological libraries are important tools in the development of new peptide-based compounds. here, we describe the use of a soluble peptide library system as a complementary tool in the field of ligand development. random peptides were expressed in s. cerevisiae as carboxy-terminal extensions of the eukaryotic initiation factor 5a (eif5a) and secreted into the culture supernatant. expression and screening of this library were performed in a microwell format. as an example of this versatile approa ...	2007	17492714
tri-cistronic cloning, overexpression and purification of human rad9, rad1, hus1 protein complex.	the least understood components of the dna damage checkpoint are the dna damage sensors. genetic studies of schizosaccharomyces pombe identified six yeast genes, rad3, rad17, rad9, rad1, hus1, and rad26, which encode proteins thought to sense dna damage and activate the checkpoint-signaling cascade. it has been suggested that rad9, rad1 and hus1 make a heterotrimeric complex forming a pcna-like structure. in order to carry out structural and biophysical studies of the complex and its associated ...	2007	17493829
differences in atp7a gene expression underlie intrafamilial variability in menkes disease/occipital horn syndrome.	pronounced intrafamilial variability is unusual in menkes disease and its variants. we report two unrelated families featuring affected members with unusually disparate clinical and biochemical phenotypes and explore the underlying molecular mechanisms.	2007	17496194
conserved c-terminal domains of mcenp-f (lek1) regulate subcellular localization and mitotic checkpoint delay.	centromeric protein-f (cenp-f) family members have been identified in organisms from yeast to human. cenp-f proteins are a component of kinetochores during mitosis, bind to the rb family of tumor suppressors, and have regulatory effects on the cell cycle and differentiation; however, their role in these processes has not been resolved. here, we provide evidence that the role of murine cenp-f (mcenp-f, also known as lek1) remains largely conserved and that the domains within the c-terminus collec ...	2007	17498689
the structure of the c-terminal domain of the protein kinase atsos2 bound to the calcium sensor atsos3.	the plant sos2 family of protein kinases and their interacting activators, the sos3 family of calcium-binding proteins, function together in decoding calcium signals elicited by different environmental stimuli. sos2 is activated by ca-sos3 and subsequently phosphorylates the ion transporter sos1 to bring about cellular ion homeostasis under salt stress. in addition to possessing the kinase activity, members of the sos2 family of protein kinases can bind to protein phosphatase 2cs. the crystal st ...	2007	17499048
characterization of the fam110 gene family.	we have previously characterized the centrosome/spindle pole-associated protein (cspp) involved in cell cycle progression. the open reading frame c20orf55 was identified in a yeast two-hybrid screen in a search for cspp-interacting proteins. a homology search revealed that c20orf55 belongs to a gene family consisting of three members that have not yet been described. the hugo nomenclature committee has assigned these genes the names fam110a-fam110c. studies of transfectants showed that the fam11 ...	2007	17499476
biochemical and mass spectrometric characterization of the human cb2 cannabinoid receptor expressed in pichia pastoris--importance of correct processing of the n-terminus.	this study was conducted to optimize the expression of human cb2 cannabinoid receptors in methylotrophic yeast pichia pastoris (p. pastoris). two major species of expressed cb2 proteins were seen on western blot, i.e., a 42 kda band which matches the calculated molecular weight for tagged cb2, and a 52/55 kda doublet. treatment of membranes with n-glycosidase f or inclusion of tunicamycin in the culture medium during induction resulted in the disappearance of the 55 kda, but not the 52 kda band, ...	2007	17500008
crystal structures of the bar-ph and ptb domains of human appl1.	appl1 interacts with adiponectin receptors and other important signaling molecules. it contains a bar and a ph domain near its n terminus, and the two domains may function as a unit (bar-ph domain). we report here the crystal structures of the bar-ph and ptb domains of human appl1. the structures reveal novel features for bar domain dimerization and for the interactions between the bar and ph domains. the bar domain dimer of appl1 contains two four-helical bundles, whereas other bar domain dimer ...	2007	17502098
the acetyltransferase activity of san stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner.	proper sister chromatid cohesion is critical for maintaining genetic stability. san is a putative acetyltransferase that is important for sister chromatid cohesion in drosophila melanogaster, but not in budding yeast. we showed that san is critical for sister chromatid cohesion in hela cells, suggesting that this mechanism may be conserved in metazoans. furthermore, although a small fraction of san interacts with the nata complex, san appears to mediate cohesion independently. san exhibits acety ...	2007	17502424
high-efficiency recovery of target cells using improved yeast display system for detection of protein-protein interactions.	we constructed a high-throughput screening (hts) system for target cells based on the detection of protein-protein interactions by flow cytometric sorting due to the improvement in the yeast cell surface display system. interaction model proteins, which are the zz domain derived from staphylococcus aureus and the fc part of human immunoglobulin g (igg), were displayed on the yeast cell surface. we achieved a rapid and enhanced expression of these proteins as a result of adopting an appropriate y ...	2007	17503034
an n-terminal nucleotide-binding site in vdac1: involvement in regulating mitochondrial function.	in a previous study, we presented evidence for the existence of a nucleotide-binding site (nbs) in the n-terminal region of the voltage-dependent anion channel (vdac1). in this study, further localization and possible roles of the proposed vdac1-nbs were investigated using site-directed mutagenesis. the predicated nbs of murine vdac1 (mvdac1) was mutated by replacing two glycine residues with alanines or a conserved lysine residue with a serine. expression of the g21a,g23a- and k20s-mvdac1s in h ...	2007	17503466
human maf1 negatively regulates rna polymerase iii transcription via the tfiib family members brf1 and brf2.	rna polymerase iii (rna pol iii) transcribes many of the small structural rna molecules involved in processing and translation, thereby regulating the growth rate of a cell. initiation of pol iii transcription requires the evolutionarily conserved pol iii initiation factor tfiiib. tfiiib is the molecular target of regulation by tumor suppressors, including p53, rb and the rb-related pocket proteins. however, our understanding of negative regulation of human tfiiib-mediated transcription by other ...	2007	17505538
the interaction of pp1 with brca1 and analysis of their expression in breast tumors.	the breast cancer susceptibility gene, brca1, is implicated in multiple cellular processes including dna repair, the transactivation of genes, and the ubiquitination of proteins; however its precise functions remain to be fully understood. identification and characterization of brca1 protein interactions may help to further elucidate the function and regulation of brca1. additionally, detection of changes in the expression levels of brca1 and its interacting proteins in primary human breast tumo ...	2007	17511879
gene essentiality, gene duplicability and protein connectivity in human and mouse.	it has previously been found that, in yeast, gene essentiality is positively correlated with protein connectivity (number of interaction partners) but negatively correlated with the existence of gene duplicates and that highly connected proteins tend to have a low gene duplicability. using data from human and mouse, we show here that, in mammals, the first of these relationships holds true, but unlike the second relationship in yeast, highly connected mammalian proteins tend to have a high gene ...	2007	17512629
split-ubiquitin two-hybrid assay to analyze protein-protein interactions at the endosome: application to saccharomyces cerevisiae bro1 interacting with escrt complexes, the doa4 ubiquitin hydrolase, and the rsp5 ubiquitin ligase.	targeting of membrane proteins into the lysosomal/vacuolar lumen for degradation requires their prior sorting into multivesicular bodies (mvb). the mvb sorting pathway depends on escrt-0, -i, -ii, and -iii protein complexes functioning on the endosomal membrane and on additional factors, such as bro1/alix and the ubiquitin ligase rsp5/nedd4. we used the split-ubiquitin two-hybrid assay to analyze the interaction partners of yeast bro1 at its natural cellular location. we show that bro1 interacts ...	2007	17513562
[neurodegenerative amyloidoses: the yeast model].	more than 20 human diseases are related to protein misfolding which causes formation of amyloids, fibrillar aggregates of normally soluble proteins. such diseases are called amyloid diseases or amyloidoses. of them only prion diseases are transmissible. amyloids of the prion type are described in lower eukaryotes. however, in contrast to mammalian prions, which cause incurable neurodegenerative diseases, prions of lower eukaryotes are related to some non-chromosomally inherited phenotypic traits ...	2007	17514901
indelscan: a web server for comparative identification of species-specific and non-species-specific insertion/deletion events.	insertion and deletion (indel) events usually have dramatic effects on genome structure and gene function. species-specific indels have been demonstrated to be associated with species-unique traits. currently, indel identifications mainly rely on pair-wise sequence alignments (the 'pair-wise indels'), which suffer lack of discrimination of species specificity and insertion versus deletion. also, there is no freely accessible web server for genome-wide identification of indels. therefore, we deve ...	2007	17517762
secretion expression and activity assay of a novel fusion protein of thrombopoietin and interleukin-6 in pichia pastoris.	thrombopoietin (tpo) is an important haematopoietic factor in megakaryocytic activities as well as in platelet production. interleukin 6 (il-6) can co-stimulate tpo-dependent formation of colony forming unit of megakaryocyte (cfu-meg) growth which could be responsible for residual platelet formation in tpo-deficient or c-mpl-deficient animals. in this report, we demonstrated the development of a high-level expression system to produce a 78-kda human fusion protein il-6/tpo (named zh646). this wa ...	2007	17517790
exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model.	candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the most common human fungal pathogen. th1 cytokines such as interleukin-2 (il-2), gamma interferon (ifn-gamma), and tumor necrosis factor alpha (tnf-alpha), which are induced by macrophage il-12, are critical to resistance against systemic candidiasis, while th2 cytokines such as il-4 and il-5 are less critical. farnesol is a quorum-sensing molecule produced by c. albicans that controls the formation of mycelia but is ...	2007	17517874
human gcip interacts with ct847, a novel chlamydia trachomatis type iii secretion substrate, and is degraded in a tissue-culture infection model.	the obligate intracellular bacterium chlamydia trachomatis occupies a parasitophorous vacuole and employs a type iii secretion mechanism to translocate host-interactive proteins. these proteins most likely contribute to pathogenesis through modulation of host cell mechanisms crucial for the establishment and maintenance of a permissive intracellular environment. using a surrogate yersinia type iii secretion system (t3ss), we have identified the conserved gene product ct847 as a chlamydial t3ss s ...	2007	17532760
human nuf2 interacts with centromere-associated protein e and is essential for a stable spindle microtubule-kinetochore attachment.	chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore, a multiprotein complex assembled onto centromeric dna of the chromosome. here, we show that homo sapiens (hs) nuf2 is required for stable kinetochore localization of centromere-associated protein e (cenp-e) in hela cells. hsnuf2 specifies the kinetochore association of cenp-e by interacting with its c-terminal domain. the region of hsnuf2 binding to cenp-e was mapped to its ...	2007	17535814
a unique and specific interaction between alphat-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.	alpha-catenins play key functional roles in cadherin-catenin cell-cell adhesion complexes. we previously reported on alphat-catenin, a novel member of the alpha-catenin protein family. alphat-catenin is expressed predominantly in cardiomyocytes, where it colocalizes with alphae-catenin at the intercalated discs. whether alphat- and alphae-catenin have specific or synergistic functions remains unknown. in this study we used the yeast two-hybrid approach to identify specific functions of alphat-ca ...	2007	17535849
real-time fluorescence detection of erad substrate retrotranslocation in a mammalian in vitro system.	secretory proteins unable to assemble into their native states in the endoplasmic reticulum (er) are transported back or "retrotranslocated" into the cytosol for er-associated degradation (erad). to examine the roles of different components in erad, one fluorescence-labeled erad substrate was encapsulated with selected lumenal factors inside mammalian microsomes. after mixing microsomes with fluorescence-quenching agents and selected cytosolic proteins, the rate of substrate efflux was monitored ...	2007	17540174
molecular identification and characterization of tcmago and tcy14 in taiwania (taiwania cryptomerioides).	mago nashi (mago) and y14 proteins are highly conserved among eukaryotes, and not only play important roles in oogenesis, embryogenesis and germ-line determination during animal development, but also participate in mrna localization and splicing in cell growth. we identified mago (tcmago) and y14 (tcy14) homologues derived from expressed sequence tags of taiwania cryptomerioides hayata seedlings. tcmago and tcy14 contain coding regions encoding 149 and 216 amino acids, respectively. multiple ami ...	2007	17545126
expression of human protein phosphatase-1 in saccharomyces cerevisiae highlights the role of phosphatase isoforms in regulating eukaryotic functions.	human (pp1) isoforms, pp1alpha, pp1beta, pp1gamma1, and pp1gamma2, differ in primary sequences at n and c termini that potentially bind cellular regulators and define their physiological functions. the glc7 gene encodes the pp1 catalytic subunit with >80% sequence identity to human pp1 and is essential for viability of saccharomyces cerevisiae. in yeast, glc7p regulates glycogen and protein synthesis, actin cytoskeleton, gene expression, and cell division. we substituted human pp1 for glc7p in y ...	2007	17545157
identification and characterization of cps1 as a hyaluronic acid synthase contributing to the pathogenesis of cryptococcus neoformans infection.	cryptococcus neoformans is a pathogenic yeast that often causes devastating meningoencephalitis in immunocompromised individuals. we have previously identified the c. neoformans cps1 gene, which is required for a capsular layer on the outer cell wall. in this report, we investigate the function of the cps1 gene and its pathogenesis. we demonstrated that treatment of yeast with either 4-methylumbelliferone or hyaluronidase resulted in a reduction of the level of c. neoformans binding to human bra ...	2007	17545316
hs1-associated protein x-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin alphavbeta6.	enhanced expression levels of integrin alphavbeta6 have been linked to more aggressive invasive carcinoma cell behavior and poorer clinical prognosis. however, how alphavbeta6 determines invasion and the dynamics of integrin alphavbeta6 regulation in tumor cells are poorly understood. we have identified the 35-kda hs1-associated protein x-1 (hax-1) protein as a novel binding partner of the beta6 cytoplasmic tail using a yeast two-hybrid screen. we show that alphavbeta6-dependent migration is blo ...	2007	17545607
huntingtin facilitates dynein/dynactin-mediated vesicle transport.	cytoplasmic dynein is a multisubunit microtubule motor complex that, together with its activator, dynactin, drives vesicular cargo toward the minus ends of microtubules. huntingtin (htt) is a vesicle-associated protein found in both neuronal and nonneuronal cells that is thought to be involved in vesicular transport. in this study, we demonstrate through yeast two-hybrid and affinity chromatography assays that htt and dynein intermediate chain interact directly; endogenous htt and dynein co-immu ...	2007	17548833
evidence that a recq helicase slows senescence by resolving recombining telomeres.	recq helicases, including saccharomyces cerevisiae sgs1p and the human werner syndrome protein, are important for telomere maintenance in cells lacking telomerase activity. how maintenance is accomplished is only partly understood, although there is evidence that recq helicases function in telomere replication and recombination. here we use two-dimensional gel electrophoresis (2dge) and telomere sequence analysis to explore why cells lacking telomerase and sgs1p (tlc1 sgs1 mutants) senesce more ...	2007	17550308
resveratrol is a class ia phosphoinositide 3-kinase inhibitor.	resveratrol, a polyphenol found in fruits, possesses chemopreventive and chemotherapeutic properties and has been shown to increase lifespan in yeast and metazoans, including mice. genetic evidence and in vitro enzymatic measurements indicate that the deacetylase sir2/sirt1, an enzyme promoting stress resistance and aging, is the target of resveratrol. similarly, down-regulation of insulin-like pathways, of which pi3k (phosphoinositide 3-kinase) is a key mediator, promotes longevity and is an at ...	2007	17550345
the fission yeast jmj2 reverses histone h3 lysine 4 trimethylation.	histone methylation regulates transcription, chromatin structure, and the epigenetic state of the cell. recent studies identified the jmjc domain as a catalytic module for histone demethylation. schizosaccharomyces pombe contains seven jmjc proteins, but it was unclear whether any of them functioned as histone demethylases. in this report, we show that the jmjc protein jmj2, which is evolutionarily conserved from yeast to human, reversed trimethylated h3-lys-4 to di- and mono-but not unmethylate ...	2007	17550896
werner helicase-interacting protein 1 binds polyubiquitin via its zinc finger domain.	dna repair is regulated on many levels by ubiquitination. in order to identify novel connections between dna repair pathways and ubiquitin signaling, we used mass spectrometry to identify proteins that interact with lysine 6-linked polyubiquitin chains. from this proteomic screen, we identified the dna repair protein wrnip1 (werner helicase-interacting protein 1), along with nucleosome assembly protein 1, as novel ubiquitin-interacting proteins. we found that a small zinc finger domain at the n ...	2007	17550899