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grip1tau, a novel pdz domain-containing transcriptional activator, cooperates with the testis-specific transcription elongation factor sii-t1.sii-t1 is a tissue-specific member of the transcription elongation factor s-ii that is expressed specifically in male germ cells. in the present study, we have identified a protein named grip1tau interacting with sii-t1 by yeast two-hybrid screening. grip1tau is a novel isoform of glutamate receptor-interacting protein 1 (grip1) that associates with the cytoplasmic domain of the alpha-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate (ampa)-type glutamate receptor. grip1tau is a testis-specific nu ...200415507123
variation in sequence and organization of splicing regulatory elements in vertebrate genes.although core mechanisms and machinery of premrna splicing are conserved from yeast to human, the details of intron recognition often differ, even between closely related organisms. for example, genes from the pufferfish fugu rubripes generally contain one or more introns that are not properly spliced in mouse cells. exploiting available genome sequence data, a battery of sequence analysis techniques was used to reach several conclusions about the organization and evolution of splicing regulator ...200415505203
interactor-mediated nuclear translocation and retention of protein phosphatase-1.protein ser/thr phosphatase-1 (pp1) is a ubiquitous eukaryotic enzyme that controls numerous cellular processes by the dephosphorylation of key regulatory proteins. pp1 is expressed in various cellular compartments but is most abundant in the nucleus. we have examined the determinants for the nuclear localization of enhanced green fluorescent protein-tagged pp1 in cos1 cells. our studies show that pp1gamma(1) does not contain a functional nuclear localization signal and that its nuclear accumula ...200415501817
characterization of mammalian ecm29, a 26 s proteasome-associated protein that localizes to the nucleus and membrane vesicles.in addition to its thirty or so core subunits, a number of accessory proteins associate with the 26 s proteasome presumably to assist in substrate degradation or to localize the enzyme within cells. among these proteins is ecm29p, a 200-kda yeast protein that contains numerous heat repeats as well as a putative vhs domain. higher eukaryotes possess a well conserved homolog of yeast ecm29p, and we produced antibodies to three peptides in the human ecm29 sequence. the antibodies show that ecm29 is ...200415496406
identification and characterization of the human ard1-nath protein acetyltransferase complex.protein acetyltransferases and deacetylases have been implicated in oncogenesis, apoptosis and cell cycle regulation. most of the protein acetyltransferases described acetylate epsilon-amino groups of lysine residues within proteins. mouse ard1 (homologue of yeast ard1p, where ard1p stands for arrest defective 1 protein) is the only known protein acetyltransferase catalysing acetylation of proteins at both alpha-(n-terminus) and epsilon-amino groups. yeast ard1p interacts with nat1p (n-acetyltra ...200515496142
probing the instabilities in the dynamics of helical fragments from mouse prpc.the first step in the formation of the protease resistant form (prpsc) of prion proteins involves a conformational transition of the monomeric cellular form of prpc to a more stable aggregation prone state prpc*. a search of pdbselect and escherichia coli and yeast genomes shows that the exact pattern of charges in helix 1 (h1) is rare. among the 23 fragments in pdbselect with the pattern of charges that match h1, 83% are helical. mapping of the rarely found (in e. coli and yeast genomes) hydrop ...200415494440
interactions between g-protein-coupled receptors and periplakin: a selective means to regulate g-protein activation.a substantial number of g-protein-coupled receptor-interacting proteins have been identified initially by the use of yeast two-hybrid screens. using the c-terminal tail of both opioid receptors and the melanin concentrating hormone receptor-1 as bait, the actin and intermediate filament-binding protein periplakin was isolated. in each case, the site of interaction is within helix viii of the receptor and periplakin limits agonist-mediated g-protein activation potentially by competing with g-prot ...200415494039
ubiquilin-1 is a novel hash-1-complexing protein that regulates levels of neuronal bhlh transcription factors in human neuroblastoma cells.the basic helix-loop-helix (bhlh) transcription factor mammalian achaete-scute homologue-1 (mash-1 in mouse and hash-1 in humans) is expressed in specific subsets of embryonic neuronal precursors of both the peripheral and central nervous systems. this gene is essential for development of olfactory and most peripheral autonomic neurons. neuro-blastoma is a pediatric malignancy derived from sympathetic nervous system precursors and hash-1 is expressed in a majority of neuroblastoma tumors and cel ...200415492808
a torrid zone on mouse chromosome 1 containing a cluster of recombinational hotspots.within the 2.38-mb ath1 region of mouse chromosome 1, 42 of 45 genetic crossovers from crosses between c57bl/6j (b6) and either c3h/hej (h) or mus spretus (spret) occurred in four zones (a-d); zone a, 100 kb long, contained a cluster of at least four recombination hotspots. f1 sperm assays indicate that within this "torrid zone" the most active hotspot (a3) can initiate recombination on h and spret but not b6 chromosomes. the a3 dna sequence contains a (g/c)ttt repeat, long stretches of a or t, ...200515489519
red yeast rice extracts suppress adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3t3-l1 cells.the effects of red yeast rice extracts (re) on adipocyte differentiation of 3t3-l1 cells were studied. re were extracted from embryonic rice fermented with red yeast (monascus ruber). these extracts significantly decreased glycerol-3-phosphate dehydrogenase (gpdh) activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. moreover, mrna expression levels of both ccaat/enhancer-binding protein (c/ebp) alpha and peroxisome proliferator-activated receptor (ppar) gamma, t ...200415488898
silent information regulator 2alpha, a longevity factor and class iii histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes.yeast silent information regulator 2 (sir2), a nicotinamide adenine dinucleotide-dependent histone deacetylase (hdac) and founding member of the hdac class iii family, functions in a wide array of cellular processes, including gene silencing, longevity, and dna damage repair. we examined whether or not the mammalian ortholog sir2 affects growth and death of cardiac myocytes. cardiac myocytes express sir2alpha predominantly in the nucleus. neonatal rat cardiac myocytes were treated with 20 mmol/l ...200415486319
genetic steps of mammalian homologous repair with distinct mutagenic consequences.repair of chromosomal breaks is essential for cellular viability, but misrepair generates mutations and gross chromosomal rearrangements. we investigated the interrelationship between two homologous-repair pathways, i.e., mutagenic single-strand annealing (ssa) and precise homology-directed repair (hdr). for this, we analyzed the efficiency of repair in mammalian cells in which double-strand break (dsb) repair components were disrupted. we observed an inverse relationship between hdr and ssa whe ...200415485900
the phosphoinositol 3,4-bisphosphate-binding protein tapp1 interacts with syntrophins and regulates actin cytoskeletal organization.syntrophins are scaffold proteins of the dystrophin glycoprotein complex (dgc), which target ion channels, receptors, and signaling proteins to specialized subcellular domains. a yeast two-hybrid screen of a human brain cdna library with the psd-95, discs-large, zo-1 (pdz) domain of gamma1-syntrophin yielded overlapping clones encoding the c terminus of tapp1, a pleckstrin homology (ph) domain-containing adapter protein that interacts specifically with phosphatidylinositol 3,4-bisphosphate (pi(3 ...200415485858
cell-specific activation of the atrial natriuretic factor promoter by pitx2 and mef2a.the pitx2 homeodomain protein is mutated in patients with axenfeld-rieger syndrome and is involved in the development of multiple organ systems, including the heart. we have examined the interaction of pitx2 isoforms with myocyte-enhancing factor 2a (mef2a), which is a known regulator of cardiac development. a direct interaction between pitx2a and mef2a was demonstrated using yeast two-hybrid and gst pull-down assays. to study the functional significance of this interaction, we used the atrial n ...200415466416
consequences of npc1 and npc2 loss of function in mammalian neurons.genetic deficiency of npc1 or npc2 results in a devastating cholesterol-glycosphingolipidosis of brain and other organs known as niemann-pick type c (npc) disease. while npc1 is a transmembrane protein believed involved in retroendocytic shuttling of substrate(s) to the golgi and possibly elsewhere in cells as part of an essential recycling/homeostatic control mechanism, npc2 is a soluble lysosomal protein known to bind cholesterol. the precise role(s) of npc1 and npc2 in endosomal-lysosomal fun ...200415465426
mediation of af4 protein function in the cerebellum by siah proteins.we have established that the gene af4, which had long been recognized as disrupted in childhood leukemia, also plays a role in the cns. af4 is mutated in the robotic mouse that is characterized by ataxia and purkinje cell loss. to determine the molecular basis of this mutation, we carried out a yeast two-hybrid screen and show that af4 binds the e3 ubiquitin ligases drosophila seven in absentia (sina) homologues (siah)-1a and siah-2 in the brain. siah-1a and af4 are expressed in purkinje cells a ...200415459319
notch-induced e2a degradation requires chip and hsc70 as novel facilitators of ubiquitination.e2a transcription factors, e12 and e47, are important regulators of lymphocyte development. notch signaling pathways have been shown to regulate e2a function by accelerating the degradation of e2a proteins through a mitogen-activated protein kinase-dependent and ubiquitin-mediated pathway. to further understand the mechanism underlying e2a ubiquitination and degradation, we conducted a yeast two-hybrid screen and identified the carboxyl terminus of hsc70-interacting protein (chip) as an e47 bind ...200415456869
mbd3l1 is a transcriptional repressor that interacts with methyl-cpg-binding protein 2 (mbd2) and components of the nurd complex.methyl-cpg-binding domain proteins 2 and 3 (mbd2 and mbd3) are transcriptional repressors that contain methyl-cpg binding domains and are components of a cpg-methylated dna binding complex named mecp1. methyl-cpg-binding protein 3-like 1 (mbd3l1) is a protein with substantial homology to mbd2 and mbd3, but it lacks the methyl-cpg binding domain. mbd3l1 interacts with mbd2 and mbd3 in vitro and in yeast two-hybrid assays. gel shift experiments with a cpg-methylated dna probe indicate that recombi ...200415456747
ubiquitin-dependent degradation of id1 and id3 is mediated by the cop9 signalosome.recently, evidence is accumulating pointing to a function of the cop9 signalosome (csn) in regulation of ubiquitination by specific ubiquitin ligases. here, we demonstrate by mammalian two-hybrid analysis that the transcriptional regulators and substrates of the ubiquitin system id1 and id3, but not id2 and id4, bind to the csn subunit csn5. pull-down experiments revealed that id3 physically interacts with the csn complex. additional far western and pull-down studies with id3 support our two-hyb ...200415451666
cdc6 requirement for spindle formation during maturation of mouse oocytes.a master regulator of dna replication, cdc6 also functions in the dna-replication checkpoint by preventing dna rereplication. cyclin-dependent kinases (cdks) regulate the amount and localization of cdc6 throughout the cell cycle; cdc6 phosphorylation after dna replication initiation leads to its proteolysis in yeast or translocation to the cytoplasm in mammals. overexpression of cdc6 during the late s phase prevents entry into the m phase by activating chek1 kinase that then inactivates cdk1/cyc ...200515385409
enkurin is a novel calmodulin and trpc channel binding protein in sperm.the trpc cation channel family has been implicated in receptor- or phospholipase c (plc)-mediated ca2+ entry into animal cells. these channels are present in mammalian sperm and are assigned a role in zp3-evoked ca2+ influx that drives acrosome reactions. however, the mechanisms controlling channel activity and coupling ca2+ entry through these channels to cellular responses are not well understood. a yeast two-hybrid screen was carried out to identify trpc-interacting proteins that would be can ...200415385169
the nad biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates sir2 activity in mammalian cells.recent studies have revealed new roles for nad and its derivatives in transcriptional regulation. the evolutionarily conserved sir2 protein family requires nad for its deacetylase activity and regulates a variety of biological processes, such as stress response, differentiation, metabolism, and aging. despite its absolute requirement for nad, the regulation of sir2 function by nad biosynthesis pathways is poorly understood in mammals. in this study, we determined the kinetics of the nad biosynth ...200415381699
human kallikrein 13 involvement in extracellular matrix degradation.the human kallikrein family is a group of 15 serine protease genes clustered on chromosome 19q13.4 and shares a high degree of homology. these proteolytic enzymes have diverse physiological functions in many different tissues. growing evidence suggests that many kallikreins are differentially expressed in cancer and may play a role in metastasis. human kallikrein gene 13 (klk13) is a member of this family and codes for a trypsin-like, secreted serine protease (hk13) that is overexpressed in ovar ...200415381110
fetal alz-50 clone 1 interacts with the human orthologue of the kelch-like ech-associated protein.the fetal alz-50 reactive clone 1 (fac1) protein exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as alzheimer's disease. using the yeast two-hybrid screen, the human orthologue of keap1 (hkeap1) was identified as a fac1 interacting protein. keap1 is an important regulator of the oxidative stress response pathway through its interaction with the nrf family of transcription factors. an interaction between full-length fac1 and ...200415379550
identification and characterization of cdc50a, cdc50b and cdc50c genes in silico.bni1p, implicated in cell polarity control and microtubule regulation during yeast budding, is the saccharomyces cerevisiae homolog of human formin-homology proteins, such as fmn1, fmn2, fhod1, fhod3, fhdc1, grid2ip, fmnl1, fmnl2, fmnl3, diaph1, diaph2, diaph3, daam1 and daam2. cdc50p is necessary for subcellular localization of bni1p and asymmetrical cell division. lem3p and ynr048wp are yeast homologs of cdc50p; however, mammalian homologs of cdc50p remained to be identified. here, we identifi ...200415375526
mis16 and mis18 are required for cenp-a loading and histone deacetylation at centromeres.centromeres contain specialized chromatin that includes the centromere-specific histone h3 variant, spcenp-a/cnp1. here we report identification of five fission yeast centromere proteins, mis14-18. mis14 is recruited to kinetochores independently of cenp-a, and, conversely, cenp-a does not require mis14 to associate with centromeres. in contrast, mis15, mis16 (strong similarity with human rbap48 and rbap46), mis17, and mis18 are all part of the cenp-a recruitment pathway. mis15 and mis17 form an ...200415369671
cd22 is a functional ligand for sh2 domain-containing protein-tyrosine phosphatase-1 in primary t cells.the intracellular src homology 2 (sh2) domain-containing protein-tyrosine phosphatase (shp-1) has been characterized as a negative regulator of t cell function, contributing to the definition of t cell receptor signaling thresholds in developing and peripheral mouse t lymphocytes. the activation of shp-1 is achieved through the engagement of its tandem sh2 domains by tyrosine-phosphorylated proteins; however, the identity of the activating ligand(s) for shp-1, within mouse primary t cells, is pr ...200415364920
ccteta, a novel soluble guanylyl cyclase-interacting protein.nitric oxide (no) transduces most of its biological effects through activation of the heterodimeric enzyme, soluble guanylyl cyclase (sgc). activation of sgc results in the production of cgmp from gtp. in this paper, we demonstrate a novel protein interaction between cct (chaperonin containing t-complex polypeptide) subunit eta and the alpha1beta1 isoform of sgc. ccteta was found to interact with the beta1 subunit of sgc via a yeast-two-hybrid screen. this interaction was then confirmed in vitro ...200415347653
tandem lim domains provide synergistic binding in the lmo4:ldb1 complex.nuclear lim-only (lmo) and lim-homeodomain (lim-hd) proteins have important roles in cell fate determination, organ development and oncogenesis. these proteins contain tandemly arrayed lim domains that bind the lim interaction domain (lid) of the nuclear adaptor protein lim domain-binding protein-1 (ldb1). we have determined a high-resolution x-ray crystal structure of lmo4, a putative breast oncoprotein, in complex with ldb1-lid, providing the first example of a tandem lim:ldb1-lid complex and ...200415343268
leukemia/lymphoma-related factor, a poz domain-containing transcriptional repressor, interacts with histone deacetylase-1 and inhibits cartilage oligomeric matrix protein gene expression and chondrogenesis.mutations in the human cartilage oligomeric matrix protein (comp) gene have been linked to the development of pseudoachondroplasia and multiple epiphyseal dysplasia. we previously cloned the promoter region of the comp gene and delineated a minimal negative regulatory element (nre) that is both necessary and sufficient to repress its promoter (issack, p. s., fang, c. h., leslie, m. p., and di cesare, p. e. (2000) j. orthop. res. 18, 345-350; issack, p. s., liu, c. j., prazak, l., and di cesare, ...200415337766
predicting protein-protein interactions using signature products.proteome-wide prediction of protein-protein interaction is a difficult and important problem in biology. although there have been recent advances in both experimental and computational methods for predicting protein-protein interactions, we are only beginning to see a confluence of these techniques. in this paper, we describe a very general, high-throughput method for predicting protein-protein interactions. our method combines a sequence-based description of proteins with experimental informati ...200515319262
defects in cell growth regulation by c18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas.in this study, endogenous long chain ceramides were measured in 32 human head and neck squamous cell carcinoma (hnscc) and 10 nonsquamous head and neck carcinoma tumor tissues, as compared with adjacent noncancerous tissues, by liquid chromatography/mass spectroscopy. interestingly, only one specific ceramide, c(18:0)-ceramide, was selectively down-regulated in the majority of hnscc tumor tissues. on the other hand, in nonsquamous tumor tissues, this selectivity for c18-ceramide was not detected ...200415317812
co-localization of trax and mea2 in golgi complex of pachytene spermatocytes in the mouse.a golgin family protein, mea2, is expressed at enhanced level in pachytene spermatocytes and is indispensable for mouse spermatogenesis. because trax was shown to interact with mea2 in yeast two-hybrid, we investigated the localization of trax in pachytene spermatocytes with immunofluorescent staining. trax was found to accumulate in the golgi complex of mid-late pachytene spermatocytes and intermingled with granular mea2 signal in the central region. in a subline of the mea2 mutant mouse, a tru ...200415314092
gpr1, a putative g-protein-coupled receptor, regulates morphogenesis and hypha formation in the pathogenic fungus candida albicans.in response to various extracellular signals, the morphology of the human fungal pathogen candida albicans switches from yeast to hypha form. here, we report that gpr1 encoding a putative g-protein-coupled receptor and gpa2 encoding a galpha subunit are required for hypha formation and morphogenesis in c. albicans. mutants lacking gpr1 (gpr1/gpr1) or gpa2 (gpa2/gpa2) are defective in hypha formation and morphogenesis on solid hypha-inducing media. these phenotypic defects in solid cultures are s ...200415302825
mutation of the mouse rad17 gene leads to embryonic lethality and reveals a role in dna damage-dependent recombination.genetic defects in dna repair mechanisms and cell cycle checkpoint (ccc) genes result in increased genomic instability and cancer predisposition. discovery of mammalian homologs of yeast ccc genes suggests conservation of checkpoint mechanisms between yeast and mammals. however, the role of many ccc genes in higher eukaryotes remains elusive. here, we report that targeted deletion of an n-terminal part of mrad17, the mouse homolog of the schizosaccharomyces pombe rad17 checkpoint clamp-loader co ...200415297881
the mouse juvenile spermatogonial depletion (jsd) phenotype is due to a mutation in the x-derived retrogene, mutp14b.the recessive juvenile spermatogonial depletion (jsd) mutation results in a single wave of spermatogenesis, followed by failure of type a spermatogonia to differentiate, resulting in adult male sterility. we have identified a jsd-specific rearrangement in the mouse homologue of the saccharomyces cerevisiae gene utp14, termed mutp14b. confirmation that mutp14b underlies the jsd phenotype was obtained by transgenic bacterial artificial chromosome (bac) rescue. we also identified a homologous gene ...200415289605
map kinase phosphatase 3 (mkp3) interacts with and is phosphorylated by protein kinase ck2alpha.mitogen-activated protein (map) kinases play a central role in controlling a wide range of cellular functions following their activation by a variety of extracellular stimuli. map kinase phosphatases (mkps) represent a subfamily of dual specificity phosphatases, which negatively regulate map kinases. although erk2 activity is regulated by its phosphorylation state, mkp3 is regulated by physical interaction with erk2, independent of its enzymatic activity (camps, m., nichols, a., gillieron, c., a ...200415284227
biological role and structural mechanism of twinfilin-capping protein interaction.twinfilin and capping protein (cp) are highly conserved actin-binding proteins that regulate cytoskeletal dynamics in organisms from yeast to mammals. twinfilin binds actin monomer, while cp binds the barbed end of the actin filament. remarkably, twinfilin and cp also bind directly to each other, but the mechanism and role of this interaction in actin dynamics are not defined. here, we found that the binding of twinfilin to cp does not affect the binding of either protein to actin. furthermore, ...200415282541
the mre11 complex and the metabolism of chromosome breaks: the importance of communicating and holding things together.the conserved mre11 complex (mre11, rad50, and nbs1) plays a role in each aspect of chromosome break metabolism. the complex acts as a break sensor and functions in the activation and propagation of signaling pathways that govern cell cycle checkpoint functions in response to dna damage. in addition, the mre11 complex influences recombinational dna repair through promoting recombination between sister chromatids. the mre11 complex is required for mammalian cell viability but hypomorphic mutants ...200415279769
transcriptional repression of target genes by leunig and seuss, two interacting regulatory proteins for arabidopsis flower development.transcription repression plays important roles in preventing crucial regulatory proteins from being expressed in inappropriate temporal or spatial domains. leunig (lug) and seuss (seu) normally act to prevent ectopic expression of the floral homeotic gene agamous in flowers. lug encodes a protein with sequence similarities to the yeast tup1 corepressor. seu encodes a plant-specific regulatory protein with sequence similarity in a conserved dimerization domain to the lim-domain binding 1/chip pro ...200415277686
purification and characterization of the human gamma-secretase complex.gamma-secretase is a member of an unusual class of proteases with intramembrane catalytic sites. this enzyme cleaves many type i membrane proteins, including the amyloid beta-protein (abeta) precursor (app) and the notch receptor. biochemical and genetic studies have identified four membrane proteins as components of gamma-secretase: heterodimeric presenilin (ps) composed of its n- and c-terminal fragments (ps-ntf/ctf), a mature glycosylated form of nicastrin (nct), aph-1, and pen-2. recent data ...200415274632
swiss-2dpage, ten years later.the swiss-2dpage database was established in 1993 and is maintained collaboratively by the swiss institute of bioinformatics (sib) and the biomedical proteomics research group (bprg) of the geneva university hospital. during these years, swiss-2dpage underwent constant modification and improvement. current content includes about 4000 identified spots corresponding to 1200 different protein entries in 36 reference maps from human, mouse, arabidopsis thaliana, dictyostelium discoideum, escherichia ...200415274128
influence of selenium induced oxidative stress on spermatogenesis and lactate dehydrogenase-x in mice testis.to evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-x (ldh-x) activity in mouse testis.200415273872
direct interaction between bkca potassium channel and microtubule-associated protein 1a.the bkca channel, a potassium channel that is allosterically activated by voltage and calcium, is expressed in both excitable and non-excitable cells. the channel plays an important role in regulating membrane excitability. the channel activity can be modulated by post-translational modifications such as phosphorylation. recently, hippocampal bkca channels were shown to be directly modulated by assembly/disassembly of the submembranous actin cytoskeleton. here, we report that the bkca channel ph ...200415251455
interaction of doppel with the full-length laminin receptor precursor protein.doppel (dpl) is a homolog of normal cellular prion protein (prpc) with unknown functions. ectopic expression of dpl in the central nervous system (cns) causes neurotoxicity and this effect is rescued by the expression of prpc. however, the molecular basis for the protective effect of prpc remains unclear. using a yeast two-hybrid system, we showed that dpl binds the full-length 37-kda laminin receptor precursor protein (lrp), one of the receptors of prpc. the interaction was also validated by im ...200415246873
mitopred: a web server for the prediction of mitochondrial proteins.mitopred web server enables prediction of nucleus-encoded mitochondrial proteins in all eukaryotic species. predictions are made using a new algorithm based primarily on pfam domain occurrence patterns in mitochondrial and non-mitochondrial locations. pre-calculated predictions are instantly accessible for proteomes of saccharomyces cerevisiae, caenorhabditis elegans, drosophila, homo sapiens, mus musculus and arabidopsis species as well as all the eukaryotic sequences in the swiss-prot and trem ...200415215413
human histone deacetylase sirt2 interacts with the homeobox transcription factor hoxa10.histone deacetylases are required for transcriptional repression in eukaryotes. saccharomyces cerevisiae has several histone deacetylases, of which ysir2p is the most conserved throughout evolution. currently, there is no report on the interacting protein partner of a human sir2 homolog, sirt2. here we show for the first time that sirt2 interacts with the homeobox transcription factor, hoxa10, which was identified in a two-hybrid screen. interactions were confirmed by co-immunoprecipitation from ...200415213244
bayesian decomposition: analyzing microarray data within a biological context.the detection and correct identification of cancer, especially at an early stage, are vitally important for patient survival and quality of life. since signaling pathways play critical roles in cancer development and metastasis, methods that reliably assess the activity of these pathways are critical to understand cancer and the response to therapy. bayesian decomposition (bd) identifies signatures of expression that can be linked directly to signaling pathway activity, allowing the changes in m ...200415208194
direct interaction of glurdelta2 with shank scaffold proteins in cerebellar purkinje cells.glutamate receptor (glur) delta2 selectively expressed in cerebellar purkinje cells plays a central role in cerebellar long-term depression (ltd), motor learning, and formation of parallel fiber synapses. by yeast two-hybrid screening, we identified members of the shank family of scaffold proteins as major glurdelta2-interacting molecules. glurdelta2 bound directly to the pdz domain of shank proteins through an internal motif in the carboxyl-terminal putative cytoplasmic domain. shank1 and shank ...200415207857
kai1 cooh-terminal interacting tetraspanin (kitenin), a member of the tetraspanin family, interacts with kai1, a tumor metastasis suppressor, and enhances metastasis of cancer.we cloned recently an alternatively spliced variant of kai1 mrna that lacked exon 7 at the cooh-terminal region and showed differences in metastasis suppression when compared with the wild-type kai1. these findings indicated that the cooh-terminal region of kai1 is critical for its metastasis suppressor function. in this study, we isolated a cdna clone of vangl1, a member of the tetraspanin protein family, which interacted specifically with the cooh-terminal cytoplasmic domain of kai1 in the yea ...200415205336
structures of the yeast ribonucleotide reductase rnr2 and rnr4 homodimers.class i ribonucleotide reductases (rnrs) catalyze the reduction of ribonucleotides to deoxyribonucleotides. eukaryotic rnrs comprise two subunits, the r1 subunit, which contains substrate and allosteric effector binding sites, and the r2 subunit, which houses a catalytically essential diiron-tyrosyl radical cofactor. in saccharomyces cerevisiae, there are two variants of the r2 subunit, called rnr2 and rnr4. rnr4 is unique in that it lacks three iron-binding residues conserved in all other r2s. ...200415196016
dna binding, but not interaction with bmal1, is responsible for dec1-mediated transcription regulation of the circadian gene mper1.dec1 (differentially expressed in chondrocytes 1) and dec2 are e-box-binding transcription factors and exhibit a circadian expression pattern. recently, both proteins were found to repress the clock/bmal1-activated e-box promoters (e.g. mper1). yeast two-hybrid assay detected interactions between bmal1 and decs. it was hypothesized that dec-mediated repression on the mper1 promoter is achieved by binding to e-box elements and interacting with bmal1. in the present study, we report that e-box bin ...200415193144
sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo.hdl-mediated reverse-cholesterol transport as well as phosphoinositide signaling are mediated through plasma membrane microdomains termed caveolae/lipid rafts. however, relatively little is known regarding mechanism(s) whereby these lipids traffic to or are targeted to caveolae/lipid rafts. since sterol carrier protein-2 (scp-2) binds both cholesterol and phosphatidylinositol, the possibility that scp-2 might interact with caveolin-1 and caveolae was examined. double immunolabeling and laser sca ...200415182174
has the yo-yo stopped? an assessment of human protein-coding gene number.since the identification of approximately 25,000 proteins from the draft human genome assembly in 2001, estimates of the total have oscillated between 30,000 and 70,000. the recently announced genome closure has not generated a consensus gene count despite this being a key parameter for many areas of biology including drug target discovery and characterization of the human proteome. contrary to earlier predictions of constitutive under-detection for eukaryotic genes, the latest model organism up ...200415174140
the ubiquitin-conjugating dna repair enzyme hr6a is a maternal factor essential for early embryonic development in mice.the saccharomyces cerevisiae rad6 protein is required for a surprising diversity of cellular processes, including sporulation and replicational damage bypass of dna lesions. in mammals, two rad6-related genes, hr6a and hr6b, encode highly homologous proteins. here, we describe the phenotype of cells and mice deficient for the mhr6a gene. just like mhr6b knockout mouse embryonic fibroblasts, mhr6a-deficient cells appear to have normal dna damage resistance properties, but mhr6a knockout male and ...200415169909
lc3, gabarap and gate16 localize to autophagosomal membrane depending on form-ii formation.rat lc3, a homologue of yeast atg8 (aut7/apg8), localizes to autophagosomal membranes after post-translational modifications. the c-terminal fragment of lc3 is cleaved immediately following synthesis to yield a cytosolic form called lc3-i. a subpopulation of lc3-i is further converted to an autophagosome-associating form, lc3-ii. because yeast atg8 is conjugated with phosphatidylethanolamine (pe) by a ubiquitin-like system, it has been hypothesized that lc3 is modified in a similar manner. here, ...200415169837
the atypical orphan nuclear receptor dax-1 interacts with orphan nuclear receptor nur77 and represses its transactivation.dax-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the x chromosome, gene 1) (nrob1) is an atypical member of the nuclear receptor family, which lacks the classical zinc finger dna binding domain and acts as a coregulator of a number of nuclear receptors. in this study, we have found that dax-1 is a novel coregulator of the orphan nuclear receptor nur77 (nr4a1). we demonstrate that dax-1 represses the nur77 transactivation by transient transfection assays. spec ...200415155786
nipbl, encoding a homolog of fungal scc2-type sister chromatid cohesion proteins and fly nipped-b, is mutated in cornelia de lange syndrome.cornelia de lange syndrome (cdls) is a multiple malformation disorder characterized by dysmorphic facial features, mental retardation, growth delay and limb reduction defects. we indentified and characterized a new gene, nipbl, that is mutated in individuals with cdls and determined its structure and the structures of mouse, rat and zebrafish homologs. we named its protein product delangin. vertebrate delangins have substantial homology to orthologs in flies, worms, plants and fungi, including s ...200415146185
nurd complex component mi-2beta binds to and represses rorgamma-mediated transcriptional activation.rorgamma is a nuclear receptor that binds to dna motifs as a monomer to constitutively activate target genes. rorgamma plays an important role in thymocyte development and lymph node organogenesis, while the regulation of rorgamma-mediated transcriptional activation is currently unclear. the purpose of this study was to identify other nuclear proteins that interact with rorgamma. a yeast two-hybrid screen with y190 yeast cells under stringent conditions resulted in the identification of chd4, al ...200415144897
visualization of the dynamics of gene expression in the living mouse.reporter genes can monitor the status and activity of recombinant genomes in a diverse array of organisms, from bacteria and yeast to plants and animals. we have combined luciferase reporter genes with a conditional gene expression system based on regulatory elements from the lac operon of escherichia coli to visualize the dynamics of gene expression in realtime in the living mouse. using this technology, we have determined the rate of gene induction and repression, the level of target gene acti ...200415142410
metal-binding mechanism of cox17, a copper chaperone for cytochrome c oxidase.cox17, a copper chaperone for cytochrome c oxidase, is an essential and highly conserved protein. the structure and mechanism of functioning of cox17 are unknown, and even its metalbinding stoichiometry is elusive. in the present study, we demonstrate, using electrospray ionization-ms, that porcine cox17 binds co-operatively four cu+ ions. cu4cox17 is stable at ph values above 3 and fluorescence spectra indicate the presence of a solvent-shielded multinuclear cu(i) cluster. combining our results ...200415142040
transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases.histone acetyltransferases and deacetylases are recruited by transcription factors and adapter proteins to regulate specific subsets of target genes. we were interested in identifying interaction partners of histone deacetylase 1 (hdac1) that might be involved in conferring target or substrate specificity. using the yeast two-hybrid system, we isolated the repressor of estrogen receptor activity (rea) as a novel hdac1-associated protein. we demonstrated the in vivo interaction of rea with hdac1 ...200415140878
early myocardial function affects endocardial cushion development in zebrafish.function of the heart begins long before its formation is complete. analyses in mouse and zebrafish have shown that myocardial function is not required for early steps of organogenesis, such as formation of the heart tube or chamber specification. however, whether myocardial function is required for later steps of cardiac development, such as endocardial cushion (ec) formation, has not been established. recent technical advances and approaches have provided novel inroads toward the study of orga ...200415138499
tale homeodomain proteins regulate gonadotropin-releasing hormone gene expression independently and via interactions with oct-1.gonadotropin-releasing hormone (gnrh) is the central regulator of reproductive function. expression of the gnrh gene is confined to a rare population of neurons scattered throughout the hypothalamus. restricted expression of the rat gnrh gene is driven by a multicomponent enhancer and an evolutionarily conserved promoter. oct-1, a ubiquitous pou homeodomain transcription factor, was identified as an essential factor regulating gnrh transcription in the gt1-7 hypothalamic neuronal cell line. in t ...200415138251
cgi-58 interacts with perilipin and is localized to lipid droplets. possible involvement of cgi-58 mislocalization in chanarin-dorfman syndrome.lipid droplets (lds) are a class of ubiquitous cellular organelles that are involved in lipid storage and metabolism. although the mechanisms of the biogenesis of lds are still unclear, a set of proteins called the pat domain family have been characterized as factors associating with lds. perilipin, a member of this family, is expressed exclusively in the adipose tissue and regulates the breakdown of triacylglycerol in lds via its phosphorylation. in this study, we used a yeast two-hybrid system ...200415136565
follistatin complexes myostatin and antagonises myostatin-mediated inhibition of myogenesis.follistatin is known to antagonise the function of several members of the tgf-beta family of secreted signalling factors, including myostatin, the most powerful inhibitor of muscle growth characterised to date. in this study, we compare the expression of myostatin and follistatin during chick development and show that they are expressed in the vicinity or in overlapping domains to suggest possible interaction during muscle development. we performed yeast and mammalian two-hybrid studies and show ...200415136138
low-density lipoprotein receptor-related protein interacts with mafb, a regulator of hindbrain development.the intracellular domain (icd) of the low-density lipoprotein receptor-related protein (lrp) functionally interacts with adaptor proteins both as an integral part of the receptor polypeptide and after proteolytic release. identification of such adaptors has been difficult because the icd is self-activating in conventional transcription factor-based yeast two-hybrid screens. we adopted an alternative screen for the icd that depends on the activation of the ras-signaling pathway and uncovered the ...200415135046
an activated mtor mutant supports growth factor-independent, nutrient-dependent cell survival.in yeast, tor couples cellular growth and metabolism to the availability of extracellular nutrients. in contrast, mammalian tor kinase activity has been reported to be regulated by growth factor stimulation via the pi3k/akt pathway. consistent with this, growth factor deprivation results in dephosphorylation of the mtor target proteins p70s6k and 4ebp1 in the face of abundant extracellular nutrients. to determine whether the activation of mtor was sufficient to support cell survival in the absen ...200415133498
monoclonal antibodies and sandwich elisa for quantitation of hm-1 killer toxin.to establish a method for quantitative analysis of hm-1 killer toxin (hm-1), two purified mouse monoclonal antibodies, 1f1 and 4a2, and rabbit polyclonal antiserum against hm-1 were prepared. both monoclonal antibodies were classified as igg1(kappa) subtype, and did not neutralize the killing activity of hm-1. by spots analysis, the epitope of 1f1 was found in the sequence of cdpntg with a corresponding sequence of 11-16 from n-terminal amino acid residues of hm-1, but the epitope of 4a2 was not ...200415133246
mitochondrial building blocks.despite many genomic and proteomic attempts, approximately half of all mitochondrial proteins remain unidentified. moreover, the composition of mitochondria varies in different mammalian cell types and the details of this tissue specificity are unclear. two recent reports provide a major advance in our understanding of mitochondrial function. sickmann et al. used an exhaustive proteomic approach and came very close to identifying the complete set of yeast mitochondrial proteins. mootha et al. ex ...200415130575
mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis.mammalian meiosis differs from that seen in lower eukaryotes in several respects, not least of which is the added complexity of dealing with chromosomal interactions across a much larger genome (12 mb over 16 chromosome pairs in saccharomyces cerevisiae compared to 2500 mb over 19 autosome pairs in mus musculus). thus, the recombination machinery, while being highly conserved through eukaryotes, has evolved to accommodate such issues to preserve genome integrity and to ensure propagation of the ...200415120996
progressive decrease in chaperone protein levels in a mouse model of huntington's disease and induction of stress proteins as a therapeutic approach.the manipulation of chaperone levels has been shown to inhibit aggregation and/or rescue cell death in saccharomyces cerevisiae, caenorhabditis elegans, drosophila melanogaster and cell culture models of huntington's disease (hd) and other polyglutamine (polyq) disorders. we show here that a progressive decrease in hdj1, hdj2, hsp70, alphasgt and betasgt brain levels likely contributes to disease pathogenesis in the r6/2 mouse model of hd. despite a predominantly extranuclear location, hdj1, hdj ...200415115766
identification of a novel binding partners for tumor suppressor pten by a yeast two-hybrid approach.to identify novel pten-binding partners.200415112574
dna double-strand breaks, recombination and synapsis: the timing of meiosis differs in grasshoppers and flies.the temporal and functional relationships between dna events of meiotic recombination and synaptonemal complex formation are a matter of discussion within the meiotic field. to analyse this subject in grasshoppers, organisms that have been considered as models for meiotic studies for many years, we have studied the localization of phosphorylated histone h2ax (gamma-h2ax), which marks the sites of double-strand breaks (dsbs), in combination with localization of cohesin smc3 and recombinase rad51. ...200415105829
identification of snapin and three novel proteins (blos1, blos2, and blos3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (bloc-1).biogenesis of lysosome-related organelles complex-1 (bloc-1) is a ubiquitously expressed multisubunit protein complex required for the normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules. the complex is known to contain the coiled-coil-forming proteins, pallidin, muted, cappuccino, and dysbindin. the genes encoding these proteins are defective in inbred mouse strains that serve as models of hermansky-pudlak syndrome (hps) ...200415102850
binding of proteins to the pdz domain regulates proteolytic activity of htra1 serine protease.htra1, a member of the mammalian htra (high temperature requirement a) serine protease family, has a highly conserved protease domain followed by a pdz domain. accumulating evidence has indicated that pdz domains regulate protease activity of htra proteins. we searched for binding partners of the pdz domain of mouse htra1 by yeast two-hybrid screening, and isolated proteins that were recognized by the htra1 pdz domain through their c-terminal ends with a core consensus phi-x-phi-[v/l/f/a]-cooh s ...200415101818
comparative analysis detects dependencies among the 5' splice-site positions.human-mouse comparative genomics is an informative tool to assess sequence functionality as inferred from its conservation level. we used this approach to examine dependency among different positions of the 5' splice site. we compiled a data set of 50,493 homologous human-mouse internal exons and analyzed the frequency of changes among different positions of homologous human-mouse 5' splice-site pairs. we found mutual relationships between positions +4 and +5, +5 and +6, -2 and +5, and -1 and +5 ...200415100438
identification and characterization of a novel bash n terminus-associated protein, bnas2.a b cell-specific adaptor protein, bash (also known as blnk or slp-65), is crucial for b cell receptor (bcr) signaling. bash binds to various signaling intermediates, such as btk, plcgamma2, vav, and grb2, through its well defined motifs. although functional significance of such interactions has been documented, bash-mediated signal transduction mechanism is not fully understood. using the yeast two-hybrid system, we have identified a novel protein that binds to a conserved n-terminal domain of ...200415087455
normal development and fertility of knockout mice lacking the tumor suppressor gene lrp1b suggest functional compensation by lrp1.lrp1b and the closely related lrp1 are large members of the low-density lipoprotein receptor family. at the protein level lrp1b is 55% identical to lrp1, a multifunctional and developmentally essential receptor with roles in cargo transport and cellular signaling. somatic lrp1b mutations frequently occur in non-small cell lung cancer and urothelial cancers, suggesting a role in the modulation of cellular growth. in contrast to lrp1, lrp1b-deficient mice develop normally, most likely due to its r ...200415082773
organization and annotation of the xcat critical region: elimination of seven positional candidate genes.xcat mice display x-linked congenital cataracts and are a mouse model for the human x-linked cataract disease nance horan syndrome (nhs). the genetic defect in xcat mice and nhs patients is not known. we isolated and sequenced a bac contig representing a portion of the xcat critical region. we combined our sequencing data with the most recent mouse sequence assemblies from both celera and public databases. the sequence of the 2.2-mb xcat critical region was then analyzed for potential xcat candi ...200415081118
neutrophil serine proteinases inactivate surfactant protein d by cleaving within a conserved subregion of the carbohydrate recognition domain.surfactant protein d (sp-d) plays important roles in innate immunity including the defense against bacteria, fungi, and respiratory viruses. because sp-d specifically interacts with neutrophils that infiltrate the lung in response to acute inflammation and infection, we examined the hypothesis that the neutrophil-derived serine proteinases (nsps): neutrophil elastase, proteinase-3, and cathepsin g degrade sp-d. all three human nsps specifically cleaved recombinant rat and natural human sp-d dode ...200415078883
a novel protein-conjugating system for ufm1, a ubiquitin-fold modifier.several studies have addressed the importance of various ubiquitin-like (ubl) post-translational modifiers. these ubls are covalently linked to most, if not all, target protein(s) through an enzymatic cascade analogous to ubiquitylation, consisting of e1 (activating), e2 (conjugating), and e3 (ligating) enzymes. in this report, we describe the identification of a novel ubiquitin-fold modifier 1 (ufm1) with a molecular mass of 9.1 kda, displaying apparently similar tertiary structure, although la ...200415071506
growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid beta precursor protein is mediated by its src homology 2 domain.the sequential processing of the familial disease gene product amyloid beta precursor protein (abetapp) by beta- and gamma-secretases generates amyloid beta, which is considered to be the pathogenic factor of alzheimer's disease, and the aid peptide (abetapp intracellular domain). the aid peptide acts as a positive regulator of apoptosis and modulates transcription and calcium release. to gain clues about the molecular mechanisms regulating the function of abetapp and aid, proteins interacting w ...200415054097
expression analysis of the human testis-specific serine/threonine kinase (tssk) homologues. a tssk member is present in the equatorial segment of human sperm.two members of the human testis-specific serine/threonine (ser/thr) kinase family, tssk 1 and tssk 2, were cloned and sequenced from a human testis adaptor-ligated cdna library using a pcr strategy. within the cdna, open reading frames (orf) were defined encoding proteins of 367 and 358 amino acids respectively, as well as conserved kinase domains typical of the superfamily of ser/thr kinases. both genes were intronless and mapped to chromosomes 5 and 22 respectively. the human and mouse homolog ...200415044604
signalling to actin assembly via the wasp (wiskott-aldrich syndrome protein)-family proteins and the arp2/3 complex.the assembly of a branched network of actin filaments provides the mechanical propulsion that drives a range of dynamic cellular processes, including cell motility. the arp2/3 complex is a crucial component of such filament networks. arp2/3 nucleates new actin filaments while bound to existing filaments, thus creating a branched network. in recent years, a number of proteins that activate the filament nucleation activity of arp2/3 have been identified, most notably the wasp (wiskott-aldrich synd ...200415040784
brca1 interacts with dominant negative swi/snf enzymes without affecting homologous recombination or radiation-induced gene activation of p21 or mdm2.brca1 is a tumor suppressor gene linked to familial breast and ovarian cancer. the brca1 protein has been implicated in a diverse set of cellular functions, including activation of gene expression by the p53 tumor suppressor and control of homologous recombination (hr) during dna repair. prior reports have demonstrated that brca1 can exist in cells in a complex with the brg1-based swi/snf atp-dependent chromatin remodeling enzymes and that swi/snf components contribute to p53-mediated gene activ ...200415034933
molecular clock and gene function.molecular phylogenies based on the molecular clock require the comparison of orthologous genes. orthologous and paralogous genes usually have very different evolutionary fates. in general, orthologs keep the same functions in species, whereas, particularly over a long time span, paralogs diverge functionally and may become pseudogenes or get lost. in eukaryotic genomes, because of the degree of redundancy of genetic information, homologous genes are grouped in gene families, the evolution of whi ...200315008425
universality and flexibility in gene expression from bacteria to human.highly parallel experimental biology is offering opportunities to not just accomplish work more easily, but to explore for underlying governing principles. recent analysis of the large-scale organization of gene expression has revealed its complex and dynamic nature. however, the underlying dynamics that generate complex gene expression and cellular organization are not yet understood. to comprehensively and quantitatively elucidate these underlying gene expression dynamics, we have analyzed gen ...200414999098
hydrophobic scale: a second parameter to elucidating various specific ligand-protein interactions.in the sequence fourier analysis (sfa) of specific interactions such as those between fibroblast growth factors (fgfs)/fgf receptors (fgfrs), bone morphogenetic proteins (bmps)/bmp receptors (bmprs), or tumor repressor protein p53/mouse double minute 2 homolog (mdm2), the characteristic frequency peak(s) could be observed with the hydrophobic scale for 20 amino acids as well as 4 nucleotides as the physicochemical parameter, but not successfully with the absolute electronegativity scale. this re ...200414993768
eukaryotic regulatory element conservation analysis and identification using comparative genomics.comparative genomics is a promising approach to the challenging problem of eukaryotic regulatory element identification, because functional noncoding sequences may be conserved across species from evolutionary constraints. we systematically analyzed known human and saccharomyces cerevisiae regulatory elements and discovered that human regulatory elements are more conserved between human and mouse than are background sequences. although s. cerevisiae regulatory elements do not appear to be more c ...200414993210
transgenic mice carrying yeast artificial chromosomes.the generation of transgenic mice with yeast artificial chromosomes (yacs) has proven to be a valuable system to: (1) study gene structure-function relationships; (2) produce mouse models of human disease; (3) complement mouse mutants; (4) generate mice bioreactors; and (5) screen yac libraries in vivo. continued refinement of current techniques and development of new protocols should encourage widespread adaptation of this strategy for these and other applications. use of whole loci as transgen ...200314987397
daxx, flash, and faf-1 modulate mineralocorticoid and glucocorticoid receptor-mediated transcription in hippocampal cells--toward a basis for the opposite actions elicited by two nuclear receptors?mineralocorticoid (mr) and glucocorticoid (gr) receptors are two closely-related members of the steroid nuclear receptor family of transcription factors that bind common ligands in the brain (corticosterone and cortisol) and supposedly have identical hormone response elements. this raises the important question of how they can elicit differential biological actions in neurons in which they are often colocalized. one plausible explanation is that they differentially recruit proteins (coregulators ...200414978255
physical and functional interactions between daxx and dna methyltransferase 1-associated protein, dmap1.daxx has been shown to play an essential role in type i ifn-alphabeta-mediated suppression of b cell development and apoptosis. recently, we demonstrated that tyk2 is directly involved in ifn signaling for the induction and translocation of daxx, which may result in growth arrest and/or apoptosis of b lymphocyte progenitors. to clarify how daxx regulates b cell development, we examined daxx interacting partners by yeast two-hybrid screening. dna methyltransferase 1 (dnmt1)-associated protein (dm ...200414978102
cnlac1 is required for extrapulmonary dissemination of cryptococcus neoformans but not pulmonary persistence.the pathogenic yeast cryptococcus neoformans produces a laccase enzyme (cnlac1), which catalyzes the synthesis of melanin in the presence of phenolic compounds. a number of genes have been implicated in the regulation of laccase and melanization, including ipc1, gpa1, met3, and ste12. albino mutants derived from random mutagenesis techniques may contain mutations in genes that regulate multiple virulence factors, including cnlac1. the goal of our study is to investigate the role of cnlac1 in vir ...200414977977
identification of a novel box c/d snorna from mouse nucleolar cdna library.by construction and screen of mouse nucleolar cdna library, a novel mammalian small nucleolar rnas (snorna) was identified. the novel snorna, 70 nt in length, displays structural features typical of c/d box snorna family. the snorna possesses an 11-nt-long rrna antisense element and is predicted to guide the 2'-o-methylation of mouse 28s rrna at g4043, a site unknown so far to be modified in vertebrates. the comparison of functional element of snorna guides among eukaryotes reveals that the nove ...200414960365
[behavior of spontaneous mouse tumors treated in vivo with year. v]. 195114846186
the galactokinase of hypocrea jecorina is essential for cellulase induction by lactose but dispensable for growth on d-galactose.lactose is the only soluble carbon source which can be used economically for the production of cellulases or heterologous proteins under cellulase expression signals by hypocrea jecorina (=trichoderma reesei). towards an understanding of lactose metabolism and its role in cellulase formation, we have cloned and characterized the gal1 (galactokinase) gene of h. jecorina, which catalyses the first step in d-galactose catabolism. it exhibits a calculated mr of 57 kda, and shows moderate identity (a ...200414763977
chromosome 1 trisomy compromises the virulence of candida albicans.although increases in chromosome copy number typically have devastating developmental consequences in mammals, fungal cells such as saccharomyces cerevisiae seem to tolerate trisomies without obvious impairment of growth. here, we demonstrate that two commonly used laboratory strains of the yeast candida albicans, cai-4 and sgy-243, can carry three copies of chromosome 1. although the trisomic strains grow well in the laboratory, ura+ derivatives of cai-4, carrying three copies of chromosome 1, ...200414756793
identification of a protein that interacts with the golli-myelin basic protein and with nuclear lim interactor in the nervous system.the myelin basic protein (mbp) gene encodes the classic mbps and the golli proteins, which are related structurally to the mbps but are not components of the myelin sheath. a yeast two-hybrid approach was used to identify molecular partners that interact with the golli proteins. a mouse cdna was cloned that encoded a protein of 261 amino acids and called golli-interacting protein (gip). database analysis revealed that gip was the murine homolog of human nuclear lim interactor-interacting factor ...200414743429
mammalian d-aspartyl endopeptidase: a scavenger for noxious racemized proteins in aging.the accumulation of d-isomers of aspartic acid (d-asp) in proteins during aging has been implicated in the pathogenesis of alzheimer's disease, cataracts, and arteriosclerosis. here, we identified a specific lactacystin-sensitive endopeptidase that cleaves the d-asp-containing protein and named it d-aspartyl endopeptidase (daep). daep has a multi-complex structure (mw: 600kda) and is localized in the inner mitochondrial membrane of mouse and rabbit, but daep activity was not detected in escheric ...200414741696
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