Publications

appl1 is dispensable for mouse development, and loss of appl1 has growth factor-selective effects on akt signaling in murine embryonic fibroblasts.	the adaptor protein appl1 (adaptor protein containing pleckstrin homology (ph), phosphotyrosine binding (ptb), and leucine zipper motifs) was first identified as a binding protein of akt2 by yeast two-hybrid screening. appl1 was subsequently found to bind to several membrane-bound receptors and was implicated in their signal transduction through akt and/or mapk pathways. to determine the unambiguous role of appl1 in vivo, we generated appl1 knock-out mice. here we report that appl1 knock-out mic ...	2010	20040596
novel folate binding protein-1 interactions in embryonic orofacial tissue.	to identify proteins with which folbp1 may interact within lipid rafts in tissue derived from embryonic orofacial tissue.	2010	20045418
developmental and cellular functions of the escrt machinery in pluricellular organisms.	escrts (endosomal sorting complexes required for transport) were first discovered in yeast and are known to be required in the biogenesis of the mvb (multivesicular body). most escrt research has been carried out in vitro using models such as yeast and mammalian cells in culture. the role of the escrts genes in endosome maturation is conserved from yeast to mammals, but little is known about their function during development in multicellular organisms. since escrts play a leading role in regulat ...	2010	20059450
dietary restriction and aging, 2009.	dietary restriction (dr) is a robust nongenetic, nonpharmacological intervention that is known to increase active and healthy lifespan in a variety of species. despite a variety of differences in the protocols and the way dr is carried out in different species, conserved relationships are emerging among multiple species. 2009 saw the field of dr mature with important mechanistic insights from multiple species. a report of lifespan extension in rapamycin-treated mice suggested that the tor pathwa ...	2010	20096035
overexpression of sirt5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1.	sir2 protein, an nad-dependent deacetylase, is localized to nucleus and is involved in life span extension by calorie restriction in yeast. in mammals, among the seven sir2 homologues (sirt1-7), sirt3, 4, and 5 are localized to mitochondria. as sirt5 mrna levels in liver are increased by fasting, the physiological role of sirt5 was investigated in liver of sirt5-overexpressing transgenic (sirt5 tg) mice. we identified carbamoyl phosphate synthetase 1 (cps1), a key enzyme of the urea cycle that c ...	2010	20097174
dysbindin regulates the transcriptional level of myristoylated alanine-rich protein kinase c substrate via the interaction with nf-yb in mice brain.	an accumulating body of evidence suggests that dtnbp1 (dysbindin) is a key susceptibility gene for schizophrenia. using the yeast-two-hybrid screening system, we examined the candidate proteins interacting with dysbindin and revealed one of these candidates to be the transcription factor nf-yb.	2010	20098743
production of novel antioxidative phenolic amides through heterologous expression of the plant's chlorogenic acid biosynthesis genes in yeast.	phenolic esters like chlorogenic acid play an important role in therapeutic properties of many plant extracts. we aimed to produce phenolic esters in baker's yeast, by expressing tobacco 4cl and globe artichoke hct. indeed yeast produced phenolic esters. however, the primary product was identified as n-(e)-p-coumaroyl-3-hydroxyanthranilic acid by nmr. this compound is an amide condensation product of p-coumaric acid, which was supplied to the yeast, with 3-hydroxyanthranilic acid, which was unex ...	2010	19941969
the role of scaffold proteins in jnk signalling.	this paper summarises how scaffold proteins affects and regulate the jnk signalling pathway. we believe that some of these scaffold proteins, by virtue of their anchoring and catalytic properties contribute to a high degree of specificity of intra cellular signalling pathways that regulate the progression through the cell cycle.	2010	19922489
comparing effects of mtr and mtert deletion on gene expression and dna damage response: a critical examination of telomere length maintenance-independent roles of telomerase.	telomerase, the essential enzyme that maintains telomere length, contains two core components, tert and tr. early studies in yeast and mouse showed that loss of telomerase leads to phenotypes only after several generations, due to telomere shortening. however, recent studies have suggested additional roles for telomerase components in transcription and the response to dna damage. to examine these potential telomere length maintenance-independent roles of telomerase components, we examined first ...	2010	19850716
identification of novel pten-binding partners: pten interaction with fatty acid binding protein fabp4.	pten is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. recent studies have also demonstrated that pten is a promising target in type ii diabetes and obesity treatment. using c-terminal pten sequence in peg202-nls as bait, yeast two-hybrid screening on mouse embryo, colon cancer, and hela cdna libraries was carried out. isolated positive clones were validated by mating assay and identified through automat ...	2010	19911253
elucidating ants in worms using genomic and bioinformatic tools--biotechnological prospects?	adenine nucleotide translocators (ants) belong to the mitochondrial carrier family (mcf) of proteins. atp production and consumption are tightly linked to ants, the kinetics of which have been proposed to play a key regulatory role in mitochondrial oxidative phosphorylation. ants are also recognized as a central component of the mitochondrial permeability transition pore associated with apoptosis. although ants have been investigated in a range of vertebrates, including human, mouse and cattle, ...	2010	19770033
microkit 3.0: an integrated database of midbody, centrosome and kinetochore.	during cell division/mitosis, a specific subset of proteins is spatially and temporally assembled into protein super complexes in three distinct regions, i.e. centrosome/spindle pole, kinetochore/centromere and midbody/cleavage furrow/phragmoplast/bud neck, and modulates cell division process faithfully. although many experimental efforts have been carried out to investigate the characteristics of these proteins, no integrated database was available. here, we present the microkit database (http: ...	2010	19783819
mapping the interaction site of prion protein and sho.	the cellular prion protein (prp(c)) is a highly conserved protein among mammals and is considered to have important cellular functions. despite decades of intensive research, however, the physiological function of prp(c) remains unclear. sho (shadoo, shadow of prion protein) and prp(c) have similar n-terminals, which suggests that the two proteins share biological functions. using truncation mutants of both proteins and yeast two-hybrid analysis, with validation by co-immunoprecipitation and sur ...	2010	19685161
characterization of steroid receptor coactivator in sea urchin, strongylocentrotus nudus, and its involvement in embryonic development.	ligand-bound nuclear receptors (nrs) recruit coactivators such as members of the p160 steroid receptor coactivator (src) family and cyclic amp responsive element binding protein (creb)-binding protein (cbp) to specific enhancer elements and activate target gene transcription. in the present study, we isolated a novel src from the sea urchin strongylocentrotus nudus (snsrc) by using the ligand-binding domain of retinoid x receptor as a bait in a yeast two-hybrid screening. the snsrc and vertebrat ...	2011	20816915
a comprehensive platform for highly multiplexed mammalian functional genetic screens.	abstract: background: genome-wide screening in human and mouse cells using rna interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. there are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. as a solution, we designed a comprehensive pla ...	2011	21548937
evolutionary plasticity determination by orthologous groups distribution.	abstract: background: genetic plasticity may be understood as the ability of a functional gene network to tolerate alterations in its components or structure. usually, the studies involving gene modifications in the course of the evolution are concerned to nucleotide sequence alterations in closely related species. however, the analysis of large scale data about the distribution of gene families in non-exclusively closely related species can provide insights on how plastic or how conserved a giv ...	2011	21586164
pinta: a web server for network-based gene prioritization from expression data.	pinta (available at http://www.esat.kuleuven.be/pinta/; this web site is free and open to all users and there is no login requirement) is a web resource for the prioritization of candidate genes based on the differential expression of their neighborhood in a genome-wide protein-protein interaction network. our strategy is meant for biological and medical researchers aiming at identifying novel disease genes using disease specific expression data. pinta supports both candidate gene prioritization ...	2011	21602267
pathogenesis of candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.	alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. in this study, we investigated the pathogenesis of candida albicans and c. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (cam) and analyzed the virulence of deletion mutants. the developing immune system of the host significantly influenced susceptibility: with increasing age, embryos became more resistant and mounted a more balanced immune response, ...	2011	21603634
gisao.db: a database for ageing research.	abstract: background: age-related gene expression patterns of homo sapiens as well as of model organisms such as mus musculus, saccharomyces cerevisiae, caenorhabditis elegans and drosophila melanogaster are a basis for understanding the genetic mechanisms of ageing. for an effective analysis and interpretation of expression profiles it is necessary to store and manage huge amounts of data in an organized way, so that these data can be accessed and processed easily. description gisao.db (genes i ...	2011	21609420
mouse knock-out of iop1 protein reveals its essential role in mammalian cytosolic iron-sulfur protein biogenesis.	iron-sulfur proteins play an essential role in a variety of biologic processes and exist in multiple cellular compartments. the biogenesis of these proteins has been the subject of extensive investigation, and particular focus has been placed on the pathways that assemble iron-sulfur clusters in the different cellular compartments. iron-only hydrogenase-like protein 1 (iop1; also known as nuclear prelamin a recognition factor like protein, or narfl) is a human protein that is homologous to nar1, ...	2011	21367862
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
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
notch- and transducin-like enhancer of split (tle)-dependent histone deacetylation explain interleukin 12 (il-12) p70 inhibition by zymosan.	the fungal analog zymosan induces il-23 and low amounts of il-12 p70. this study addresses the molecular mechanisms underlying this cytokine pattern in human monocyte-derived dendritic cells. the transcriptional regulation of il23a, one of the chains of il-23, depended on the activation of c-rel and histone h3 phosphorylation, as judged from the association of c-rel with the il23a promoter and the correlation between il-23 production and ser-10-histone h3 phosphorylation. consistent with its red ...	2011	21402701
fez2 has acquired additional protein interaction partners relative to fez1: functional and evolutionary implications.	the fez (fasciculation and elongation protein zeta) family designation was purposed by bloom and horvitz by genetic analysis of c. elegans unc-76. similar human sequences were identified in the expressed sequence tag database as fez1 and fez2. the unc-76 function is necessary for normal axon fasciculation and is required for axon-axon interactions. indeed, the loss of unc-76 function results in defects in axonal transport. the human fez1 protein has been shown to rescue defects caused by unc-76 ...	2011	21408165
wwp2 is essential for palatogenesis mediated by the interaction between sox9 and mediator subunit 25.	sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. mutations in or around the sox9 gene cause campomelic dysplasia or pierre robin sequence. however, sox9-dependent transcriptional control in chondrogenesis remains largely unknown. here we identify wwp2 as a direct target of sox9. wwp2 interacts physically with sox9 and is associated with sox9 transcriptional activity via its nuclear translocation. a yeast two-hy ...	2011	21427722
the e3 ubiquitin ligase- and protein phosphatase 2a (pp2a)-binding domains of the alpha4 protein are both required for alpha4 to inhibit pp2a degradation.	protein phosphatase 2a (pp2a) is regulated through a variety of mechanisms, including post-translational modifications and association with regulatory proteins. alpha4 is one such regulatory protein that binds the pp2a catalytic subunit (pp2ac) and protects it from polyubiquitination and degradation. alpha4 is a multidomain protein with a c-terminal domain that binds mid1, a putative e3 ubiquitin ligase, and an n-terminal domain containing the pp2ac-binding site. in this work, we present the str ...	2011	21454489
recognition of yeast nucleic acids triggers a host protective type i interferon response.	although type i interferons (ifn-α/β) have been traditionally associated with antiviral responses, their importance in host defense against bacterial pathogens is being increasingly appreciated. little is known, however, about the occurrence and functional role of ifn-α/β production in response to pathogenic yeasts. here we found that conventional dendritic cells, but not macrophages or plasmacytoid dendritic cells, mounted ifn-β responses after in vitro stimulation with candida spp. or saccharo ...	2011	21480215
the cdc14b phosphatase displays oncogenic activity mediated by the ras-mek signaling pathway.	cdc14 is a dual-specific phosphatase with relevant functions during mitotic exit in yeast. the relevance of vertebrate cdc14 phosphatases is not well understood due to the presence of two paralogs, cdc14a and cdc14b, and their dispensability for cell cycle progression. here, we report that overexpression of mammalian cdc14b, but not cdc14a, leads to dramatic changes in morphology and malignant transformation of normal murine fibroblasts. cdc14b disrupts the cytoskeletal f-actin organization with ...	2011	21502810
pch2 modulates chromatid partner choice during meiotic double-strand break repair in saccharomyces cerevisiae.	in most organisms, the segregation of chromosomes during the first meiotic division is dependent upon at least one co between each pair of homologous chromosomes. cos can result from chromosome double strand breaks (dsbs) that are induced and preferentially repaired using the homologous chromosome as a template. the pch2 gene of budding yeast is required to establish proper meiotic chromosome axis structure and to regulate meiotic interhomolog dsb repair outcomes. these roles appear conserved in ...	2011	21515575
sprouty is a cytoplasmic target of adenoviral e1a oncoproteins to regulate the receptor tyrosine kinase signalling pathway.	abstract: background: oncoproteins encoded by the early region of adenoviruses have been shown to be powerful tools to study gene regulatory mechanisms, which affect major cellular events such as proliferation, differentiation, apoptosis and oncogenic transformation. they are possesing a key role to favor viral replication via their interaction with multiple cellular proteins. in a yeast two-hybrid screen we have identified sprouty1 (spry1) as a target of adenoviral e1a oncoproteins. spry protei ...	2011	21518456
histone chaperone spt6 is required for class switch recombination but not somatic hypermutation.	activation-induced cytidine deaminase (aid) is shown to be essential and sufficient to induce two genetic alterations in the ig loci: class switch recombination (csr) and somatic hypermutation (shm). however, it is still unknown how a single-molecule aid differentially regulates csr and shm. here we identified spt6 as an aid-interacting protein by yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry. knockdown of spt6 resulted in severe reduction of csr in both the en ...	2011	21518874
a survey of metabolic databases emphasizing the metacyc family.	thanks to the confluence of genome sequencing and bioinformatics, the number of metabolic databases has expanded from a handful in the mid-1990s to several thousand today. these databases lie within distinct families that have common ancestry and common attributes. the main families are the metacyc, kegg, reactome, model seed, and bigg families. we survey these database families, as well as important individual metabolic databases, including multiple human metabolic databases. the metacyc family ...	2011	21523460
autophagy process is associated with anti-neoplastic function.	autophagy is a highly conserved process of cellular degradation, which is present in yeast, plants, and mammals. under normal physiological conditions, autophagy acts to maintain cellular homeostasis and regulate the turnover of organelles. in response to cellular stresses, autophagy prevents the accumulation of impaired proteins and organelles, which serves to inhibit carcinogenesis. on this basis, it is widely accepted that most tumor suppressors, such as beclin 1 associated proteins, forkhead ...	2011	21525017
activation of the innate immune receptor dectin-1 upon formation of a 'phagocytic synapse'.	innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. dectin-1 (also known as clec7a) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ros). in contrast to inf ...	2011	21525931
secretory carrier membrane protein 2 regulates exocytic insertion of nkcc2 into the cell membrane.	the renal-specific na-k-2cl co-transporter, nkcc2, plays a pivotal role in regulating body salt levels and blood pressure. nkcc2 mutations lead to type i bartter syndrome, a life-threatening kidney disease. regulation of nkcc2 trafficking behavior serves as a major mechanism in controlling nkcc2 activity across the plasma membrane. however, the identities of the protein partners involved in cell surface targeting of nkcc2 are largely unknown. to gain insight into these processes, we used a yeast ...	2011	21205824
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
ploidy dictates repair pathway choice under dna replication stress.	this study reports an unusual ploidy-specific response to replication stress presented by a defective minichromosome maintenance (mcm) helicase allele in yeast. the corresponding mouse allele, mcm4(chaos3), predisposes mice to mammary gland tumors. while mcm4(chaos3) causes replication stress in both haploid and diploid yeast, only diploid mutants exhibit g2/m delay, severe genetic instability (gin), and reduced viability. these different outcomes are associated with distinct repair pathways ado ...	2011	21242538
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
coda (crossover distribution analyzer): quantitative characterization of crossover position patterns along chromosomes.	during meiosis, homologous chromosomes exchange segments via the formation of crossovers. this phenomenon is highly regulated; in particular, crossovers are distributed heterogeneously along the physical map and rarely arise in close proximity, a property referred to as "interference". crossover positions form patterns that give clues about how crossovers are formed. in several organisms including yeast, tomato, arabidopsis, and mouse, it is believed that crossovers form via at least two pathway ...	2011	21251248
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
cell biology. why starving cells eat themselves.		2011	21273476
okazaki fragment maturation: nucleases take centre stage.	completion of lagging strand dna synthesis requires processing of up to 50 million okazaki fragments per cell cycle in mammalian cells. even in yeast, the okazaki fragment maturation happens approximately a million times during a single round of dna replication. therefore, efficient processing of okazaki fragments is vital for dna replication and cell proliferation. during this process, primase-synthesized rna/dna primers are removed, and okazaki fragments are joined into an intact lagging stran ...	2011	21278448
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
flybow: genetic multicolor cell labeling for neural circuit analysis in drosophila melanogaster.	to facilitate studies of neural network architecture and formation, we generated three drosophila melanogaster variants of the mouse brainbow-2 system, called flybow. sequences encoding different membrane-tethered fluorescent proteins were arranged in pairs within cassettes flanked by recombination sites. flybow combines the gal4-upstream activating sequence binary system to regulate transgene expression and an inducible modified flp-frt system to drive inversions and excisions of cassettes. thi ...	2011	21297619
lysine residue 185 of rad1 is a topological but not a functional counterpart of lysine residue 164 of pcna.	monoubiquitylation of the homotrimeric dna sliding clamp pcna at lysine residue 164 (pcna(k164)) is a highly conserved, dna damage-inducible process that is mediated by the e2/e3 complex rad6/rad18. this ubiquitylation event recruits translesion synthesis (tls) polymerases capable of replicating across damaged dna templates. besides pcna, the rad6/rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric dna sliding clamp composed of rad9, rad1, and hus1 in a dna dam ...	2011	21304913
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
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
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
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
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
mitochondrial phosphatase ptpmt1 is essential for cardiolipin biosynthesis.	ptpmt1 was the first protein tyrosine phosphatase found localized to the mitochondria, but its biological function was unknown. herein, we demonstrate that whole body deletion of ptpmt1 in mice leads to embryonic lethality, suggesting an indispensable role for ptpmt1 during development. ptpmt1 deficiency in mouse embryonic fibroblasts compromises mitochondrial respiration and results in abnormal mitochondrial morphology. lipid analysis of ptpmt1-deficient fibroblasts reveals an accumulation of p ...	2011	21641550
substitution patterns are gc-biased in divergent sequences across the metazoans.	the fastest-evolving regions in the human and chimpanzee genomes show a remarkable excess of weak (a,t) to strong (g,c) nucleotide substitutions since divergence from their common ancestor. we investigated the phylogenetic extent and possible causes of this weak to strong (w ôåæ s) bias in divergent sequences (bds) using recently sequenced genomes and recombination maps from eight trios of eukaryotic species. to quantify evidence for bds, we inferred substitution histories using an efficient max ...	2011	21670083
ddx60, a dexd/h box helicase, is a novel antiviral factor promoting rig-i-like receptor-mediated signaling.	the cytoplasmic viral rna sensors rig-i and mda5 are important for the production of type i interferon and other inflammatory cytokines. ddx60 is an uncharacterized dexd/h box rna helicase similar to s. cerevisiae ski2, a cofactor of rna exosome, a protein complex required for the integrity of cytoplasmic rna. the expression of ddx60 increases after viral infection, and the protein localizes at cytoplasmic region. after viral infection, the ddx60 protein binds to endogenous rig-i protein. the pr ...	2011	21791617
mitochondrial transporter atp binding cassette mitochondrial erythroid is a novel gene required for cardiac recovery after ischemia/reperfusion.	background- oxidative stress and mitochondrial dysfunction are central mediators of cardiac dysfunction after ischemia/reperfusion. atp binding cassette mitochondrial erythroid (abc-me; abcb10; mabc2) is a mitochondrial transporter highly induced during erythroid differentiation and predominantly expressed in bone marrow, liver, and heart. until now, abc-me function in heart was unknown. several lines of evidence demonstrate that the yeast ortholog of abc-me protects against increased oxidative ...	2011	21788586
genetic evidence that synaptonemal complex axial elements govern recombination pathway choice in mice.	chiasmata resulting from interhomolog recombination are critical for proper chromosome segregation at meiotic metaphase i, thus preventing aneuploidy and consequent deleterious effects. recombination in meiosis is driven by programmed induction of double strand breaks (dsbs), and the repair of these breaks occurs primarily by recombination between homologous chromosomes, not sister chromatids. almost nothing is known about the basis for recombination partner choice in mammals. we addressed this ...	2011	21750255
legionella pneumophilarequires polyamines for optimal intracellular growth.	the gram-negative intracellular pathogen legionella pneumophilareplicates in a membrane-bound compartment known as the legionella-containing vacuole (lcv), into which it abundantly releases its chaperonin, htpb. to determine whether htpb remains within the lcv or reaches the host cell cytoplasm, we infected u937 human macrophages and cho cells with l. pneumophilaexpressing a translocation reporter consisting of the bordetella pertussisadenylate cyclase fused to htpb. these infections led to incr ...	2011	21742865
saccharomyces as a vaccine against systemic aspergillosis: 'the friend of man' a friend again?	the mortality of clinical aspergillus infections necessitates consideration of the utility of a vaccine. we have found that saccharomyces species can act as a protective vaccine against a lethal systemic aspergillus infection, and describe experiments optimizing a subcutaneous regimen with killed yeast. three injections of 2.5 mg given a week apart, 2 weeks prior to challenge, consistently, significantly, provided survival protection and reduction of infection in organs in survivors. the protect ...	2011	21825307
sirt6 promotes dna repair under stress by activating parp1.	sirtuin 6 (sirt6) is a mammalian homolog of the yeast sir2 deacetylase. mice deficient for sirt6 exhibit genome instability. here, we show that in mammalian cells subjected to oxidative stress sirt6 is recruited to the sites of dna double-strand breaks (dsbs) and stimulates dsb repair, through both nonhomologous end joining and homologous recombination. our results indicate that sirt6 physically associates with poly[adenosine diphosphate (adp)-ribose] polymerase 1 (parp1) and mono-adp-ribosylate ...	2011	21680843
ammonia-induced autophagy is independent of ulk1/ulk2 kinases.	autophagy, a lysosome-mediated catabolic process, contributes to maintenance of intracellular homeostasis and cellular response to metabolic stress. in yeast, genes essential to the execution of autophagy have been defined, including autophagy-related gene 1 (atg1), a kinase responsible for initiation of autophagy downstream of target of rapamycin. here we investigate the role of the mammalian atg1 homologs, uncoordinated family member (unc)-51-like kinase 1 and 2 (ulk1 and ulk2), in autophagy b ...	2011	21690395
comparative analysis of proteome and transcriptome variation in mouse.	the relationships between the levels of transcripts and the levels of the proteins they encode have not been examined comprehensively in mammals, although previous work in plants and yeast suggest a surprisingly modest correlation. we have examined this issue using a genetic approach in which natural variations were used to perturb both transcript levels and protein levels among inbred strains of mice. we quantified over 5,000 peptides and over 22,000 transcripts in livers of 97 inbred and recom ...	2011	21695224
hepatocyte dna replication in growing liver requires either glutathione or a single allele of txnrd1.	ribonucleotide reductase (rnr) activity requires an electron donor, which in bacteria, yeast, and plants is usually either reduced thioredoxin (trx) or reduced glutaredoxin. mice lacking glutathione reductase are viable and, although mice lacking thioredoxin reductase 1 (trxr1) are embryonic-lethal, several studies have shown that mouse cells lacking the txnrd1 gene, encoding trxr1, can proliferate normally. to better understand the in vivo electron donor requirements for mammalian rnr, we here ...	2011	22198266
ATM controls meiotic double-strand-break formation.	In many organisms, developmentally programmed double-strand breaks (DSBs) formed by the SPO11 transesterase initiate meiotic recombination, which promotes pairing and segregation of homologous chromosomes. Because every chromosome must receive a minimum number of DSBs, attention has focused on factors that support DSB formation. However, improperly repaired DSBs can cause meiotic arrest or mutation; thus, having too many DSBs is probably as deleterious as having too few. Only a small fraction of ...	2011	22002603
The plasma membrane-associated GTPase Rin interacts with the dopamine transporter and is required for protein kinase C-regulated dopamine transporter trafficking.	Dopaminergic signaling and plasticity are essential to numerous CNS functions and pathologies, including movement, cognition, and addiction. The amphetamine- and cocaine-sensitive dopamine (DA) transporter (DAT) tightly controls extracellular DA concentrations and half-life. DAT function and surface expression are not static but are dynamically modulated by membrane trafficking. We recently demonstrated that the DAT C terminus encodes a PKC-sensitive internalization signal that also suppresses b ...	2011	21957239
The role of ?6-desaturase acyl-carrier specificity in the efficient synthesis of long-chain polyunsaturated fatty acids in transgenic plants.	The role of acyl-CoA-dependent ?6-desaturation in the heterologous synthesis of omega-3 long-chain polyunsaturated fatty acids was systematically evaluated in transgenic yeast and Arabidopsis thaliana. The acyl-CoA ?6-desaturase from the picoalga Ostreococcus tauri and orthologous activities from mouse (Mus musculus) and salmon (Salmo salar) were shown to generate substantial levels of ?6-desaturated acyl-CoAs, in contrast to the phospholipid-dependent ?6-desaturases from higher plants that fail ...	2011	21902798
Antagonists of anaphase-promoting complex (APC)-2-cell cycle and apoptosis regulatory protein (CARP)-1 interaction are novel regulators of cell growth and apoptosis.	CARP-1/CCAR1, a perinuclear phosphoprotein, is a regulator of cell growth and apoptosis signaling. Although CARP-1 is a regulator of chemotherapy-dependent apoptosis, it is also a part of the NF-?B proteome and a co-activator of steroid/thyroid nuclear receptors as well as ß-catenin signaling. Our yeast two-hybrid screen revealed CARP-1 binding with the anaphase-promoting complex/cyclosome E3 ubiquitin ligase component APC-2 protein. CARP-1 also binds with anaphase-promoting complex/cyclosome co ...	2011	21903591
additive functions in boolean models of gene regulatory network modules.	gene-on-gene regulations are key components of every living organism. dynamical abstract models of genetic regulatory networks help explain the genome's evolvability and robustness. these properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. with advances in biology, some effort was deployed to dev ...	2011	22132067
translational regulation of the cell cycle: when, where, how and why?	translational regulation contributes to the control of archetypal and specialized cell cycles, such as the meiotic and early embryonic cycles. late meiosis and early embryogenesis unfold in the absence of transcription, so they particularly rely on translational repression and activation of stored maternal mrnas. here, we present examples of cell cycle regulators that are translationally controlled during different cell cycle and developmental transitions in model organisms ranging from yeast to ...	2011	22084390
dantrolene is neuroprotective in huntington's disease transgenic mouse model.	huntington's disease (hd) is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (msns). our group has previously demonstrated that calcium (ca2+) signaling is abnormal in msns from the yeast artificial chromosome transgenic mouse model of hd (yac128). moreover, we demonstrated that deranged intracellular ca2+ signaling sensitizes yac128 msns to glutamate-induced excito ...	2011	22118545
elevated levels of renal and circulating nop-7-associated 2 (nsa2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy.	aims/hypothesis: we previously found that nop-7-associated 2 (nsa2), which is involved in ribosomal biogenesis in yeast and is a putative cell cycle regulator in mammalian cells, is elevated in the kidney of goto-kakizaki (gk) rat, a spontaneous model of type 2 diabetes. here we tested the hypothesis that elevated nsa2 is involved in diabetic nephropathy (dn). methods: we examined nsa2/nsa2 expression and nsa2 pr ...	2011	22095236
importin alpha2-interacting proteins with nuclear roles during mammalian spermatogenesis.	spermatogenesis, the process of generating haploid sperm capable of fertilizing the female gamete, requires the timely transport into the nucleus of transcription and chromatin-remodeling factors, mediated by members of the importin (imp) superfamily. previous imp expression profiling implies a role for impalpha2 in testicular germ cells late in spermatogenesis. to identify interacting proteins of impalpha2 that are potential drivers of germ cell development, we performed yeast two-hybrid screen ...	2011	21900684
alfa-class prefoldin protein uxt is a novel interacting partner of amyotrophic lateral sclerosis 2 (als2) protein.	mutations in als2 gene cause several autosomal recessive forms of motor neuron diseases including juvenile amyotrophic lateral sclerosis (jals), juvenile primary lateral sclerosis (plsj) and infantile-onset ascending hereditary spastic paralysis (iahsp). to find novel protein-protein interactions of als2 protein we performed a yeast two hybrid screen and fished out the ubiquitously expressed transcript (uxt) protein. uxt is a novel gene encoding for an α-class prefoldin type chaperone which acts ...	2011	21907703
heterochromatin maintenance and establishment: lessons from the mouse pericentromere.	defined as a chromatin structure that remains condensed throughout the cell cycle heterochromatin is generally transcriptionally silent and is characterized by a specific molecular signature. constitutive heterochromatin at the pericentromere is a conserved feature throughout evolution, which impacts genome stability. here, we will summarize recent advances in our understanding of the dynamics of mouse pericentric heterochromatin during the cell cycle and development. comparison with heterochrom ...	2011	21941119
intestinal resident yeast candida glabrata requires cyb2p-mediated lactate assimilation to adapt in mouse intestine.	the intestinal resident candida glabrata opportunistically infects humans. however few genetic factors for adaptation in the intestine are identified in this fungus. here we describe the c. glabrata cyb2 gene encoding lactate dehydrogenase as an adaptation factor for survival in the intestine. cyb2 was identified as a virulence factor by a silkworm infection study. to determine the function of cyb2, we analysed in vitro phenotypes of the mutant δcyb2. the δcyb2 mutant grew well in glucose medium ...	2011	21931845
hepatic sirt1 deficiency in mice impairs mtorc2/akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance.	insulin resistance is a major risk factor for type 2 diabetes mellitus. the protein encoded by the sirtuin 1 (sirt1) gene, which is a mouse homolog of yeast sir2, is implicated in the regulation of glucose metabolism and insulin sensitivity; however, the underlying mechanism remains elusive. here, using mice with a liver-specific null mutation of sirt1, we have identified a signaling pathway involving sirt1, rictor (a component of mtor complex 2 [mtorc2]), akt, and foxo1 that regulates gluconeog ...	2011	21965330
Twinfilin-2a is dispensable for mouse development.	Twinfilins are evolutionarily conserved regulators of cytoskeletal dynamics. They inhibit actin polymerization by binding both actin monomers and filament barbed ends. Inactivation of the single twinfilin gene from budding yeast and fruit fly results in defects in endocytosis, cell migration, and organization of the cortical actin filament structures. Mammals express three twinfilin isoforms, of which twinfilin-1 and twinfilin-2a display largely overlapping expression patterns in non-muscle tiss ...	2011	21876732
a novel interaction between glycogen synthase kinase-3α (gsk-3α) and the scaffold protein receptor for activated c-kinase 1 (rack1) regulates the circadian clock.	glycogen synthase kinase-3α (gsk-3α) and gsk-3β are intracellular kinases with largely redundant functions. however, the deletion of each gsk-3 isoform in the mouse has distinct consequences, suggesting that these related enzymes also have non-overlapping isoform-specific functions. a yeast two-hybrid screen for gsk-3α interacting partners revealed an interaction with the receptor for activated c-kinase 1 (rack1). we confirm this interaction in mammalian cells, and provide evidence that rack1 do ...	2011	22187666
caffeine abolishes the ultraviolet-induced rev3 translesion replication pathway in mouse cells.	when a replicative dna polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s), which insert nucleotide(s) opposite the lesion. using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed uv-induced translesion replication (uv-tls) into two types. in human cancer cells or xeroderma pigmentosum variant (xp-v) cells, uv-tls was inhibited by caffeine or proteasome inhibitor ...	2011	22272088
safety evaluation of a proprietary food-grade, dried fermentate preparation of saccharomyces cerevisiae.	a safety evaluation was performed for epicor, a product produced by a proprietary fermentation process using saccharomyces cerevisiae. studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome p450 ([cyp] cyp1a2 and cyp3a4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. no evidence of genotoxicity or mitogenicity was s ...	2012	22222580
roles of candida albicans gat2, a gata-type zinc finger transcription factor, in biofilm formation, filamentous growth and virulence.	candida albicans is the most common human fungal pathogen, causing not only superficial infections, but also life-threatening systemic disease. c. albicans can grow in several morphological forms including unicellular yeast-form, elongated hyphae and pseudohyphae. in certain natural environments, c. albicans also exists as biofilms, which are structured and surface-attached microbial communities. transcription factors play a critical role in morphogenesis and biofilm development. in this study, ...	2012	22276126
Ex Vivo and In Vivo Inhibition of Human Rhinovirus Replication by a New Pseudosubstrate of Viral 2A Protease.	Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A(pro)) and inhibited its activity. This peptide was chemically modified with a reactiv ...	2012	22072773
the n-terminal replacement of an olfactory receptor for the development of a yeast-based biomimetic odor sensor.	for the development of a biomimetic odor-sensing system, we investigated the effects of replacing the n-terminus of an olfactory receptor (or) on its functional expression in the budding yeast, saccharomyces cerevisiae. using the mouse olfactory receptor or226 (mor226), three types of chimeric ors were constructed by replacing n-terminal regions of mor226 with the corresponding regions of the rat i7 receptor, which is known to be functionally expressed in yeast. the replacement of the n-terminal ...	2012	21915853
gonuts: the gene ontology normal usage tracking system.	the gene ontology normal usage tracking system (gonuts) is a community-based browser and usage guide for gene ontology (go) terms and a community system for general go annotation of proteins. gonuts uses wiki technology to allow registered users to share and edit notes on the use of each term in go, and to contribute annotations for specific genes of interest. by providing a site for generation of third-party documentation at the granularity of individual terms, gonuts complements the official d ...	2012	22110029