Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug resistance. Here, we defined the targets and mechanisms of antifungal action of the immunosuppressant rapamycin in ... More
Procollagen with skipping of alpha 1(I) exon 41 has lower binding affinity for alpha 1(I) C-telopeptide, impaired in vitro fibrillogenesis, and altered fibril morphology.
Previous in vitro data on type I collagen self-assembly into fibrils suggested that the amino acid 776-796 region of the alpha1(I) chain is crucial for fibril formation because it serves as the recognition site for the telopeptide of a docking collagen monomer. We used a natural collagen mutation with a ... More
Molecular characterization of Ancylostoma inhibitors of coagulation factor Xa. Hookworm anticoagulant activity in vitro predicts parasite bloodfeeding in vivo.
'Bloodfeeding hookworms, which currently infect over a billion people in the developing world, are a leading cause of gastrointestinal hemorrhage and iron deficiency anemia. The major anticoagulant inhibitor of coagulation factor Xa has been identified from the hookworm parasite Ancylostoma ceylanicum using reverse transcription PCR and 3''-rapid amplification of cDNA ... More
'Cdc25 phosphatases are dual specificity phosphatases that dephosphorylate and activate cyclin-dependent kinases (CDKs), thereby effecting the progression from one phase of the cell cycle to the next. Despite its central role in the cell cycle, relatively little is known about the catalytic mechanism of Cdc25. In order to provide insights ... More
The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM.
AuthorsSayos J, Wu C, Morra M, Wang N, Zhang X, Allen D, van Schaik S, Notarangelo L, Geha R, Roncarolo MG, Oettgen H, De Vries JE, Aversa G, Terhorst C
JournalNature
PubMed ID9774102
'In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on ... More
Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi.
Authors Gervais François G; Singaraja Roshni; Xanthoudakis Steven; Gutekunst Claire-Anne; Leavitt Blair R; Metzler Martina; Hackam Abigail S; Tam John; Vaillancourt John P; Houtzager Vicky; Rasper Dita M; Roy Sophie; Hayden Michael R; Nicholson Donald W;
JournalNat Cell Biol
PubMed ID11788820
'In Huntington disease, polyglutamine expansion of the protein huntingtin (Htt) leads to selective neurodegenerative loss of medium spiny neurons throughout the striatum by an unknown apoptotic mechanism. Binding of Hip-1, a protein normally associated with Htt, is reduced by polyglutamine expansion. Free Hip-1 binds to a hitherto unknown polypeptide, Hippi ... More
Efficient bacterial transcription of DNA nanocircle vectors with optimized single-stranded promoters.
Authors Ohmichi Tatsuo; Maki Angele; Kool Eric T;
JournalProc Natl Acad Sci U S A
PubMed ID11752404
'We describe experiments aimed at establishing whether circular single-stranded DNAs can form promoters for bacterial transcription from small folded motifs. In vitro selection experiments were carried out on circular 103-nt DNA libraries encoding 40-nt randomized sequences as well as self-processing hammerhead ribozymes. Rounds of rolling circle transcription, reverse transcription-PCR, and ... More
Evolution of genetic mechanisms controlling petal development.
AuthorsKramer EM, Irish VF
JournalNature
PubMed ID10335842
'Molecular genetic studies in Arabidopsis thaliana and other higher- eudicot flowering plants have led to the development of the ''ABC'' model of the determination of organ identity in flowers, in which three classes of gene, A, B and C, are thought to work together to determine organ identity. According to ... More
Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.
AuthorsKitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y
JournalNature Genetics
PubMed ID10319867
'Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia. Cytogenetic studies indicate that cells from affected patients show genomic instability often associated with chromosomal rearrangements causing an acquired ... More
RGS6 Interacts with SCG10 and Promotes Neuronal Differentiation. ROLE OF THE G GAMMA SUBUNIT-LIKE (GGL) DOMAIN OF RGS6.
Authors Liu Zhengyu; Chatterjee Tapan K; Fisher Rory A;
JournalJ Biol Chem
PubMed ID12140291
'RGS proteins comprise a large family of proteins named for their ability to negatively regulate heterotrimeric G protein signaling. RGS6 is a member of the R7 RGS protein subfamily endowed with DEP (disheveled, Egl-10, pleckstrin) and GGL (G protein gamma subunit-like) domains in addition to the RGS domain present in ... More
Reuptake of extracellular amelogenin by dental epithelial cells results in increased levels of amelogenin mRNA through enhanced mRNA stabilization.
'Amelogenin is an extracellular matrix protein secreted by ameloblasts and is a major component of enamel matrix. Recently, in addition to their role in enamel formation, the biological activity of enamel proteins in the process of cell differentiation has recently become widely appreciated. In this study, we examined the biological ... More
Defects in auxiliary redox proteins lead to functional methionine synthase deficiency.
AuthorsGulati S, Chen Z, Brody LC, Rosenblatt DS, Banerjee R
JournalJ Biol Chem
PubMed ID9235907
'Methionine synthase catalyzes a methyl transfer reaction from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate and is dependent on methylcobalamin, a derivative of vitamin B12, for activity. Due to the lability of the intermediate, cob(I)alamin, the activity of methionine synthase is additionally dependent on a redox activation system. In ... More
A novel zinc finger transcription factor with two isoforms that are differentially repressed by estrogen receptor-alpha.
Authors Conroy Andrew T; Sharma Manju; Holtz Ann E; Wu Chengbiao; Sun Zijie; Weigel Ronald J;
JournalJ Biol Chem
PubMed ID11779858
'Estrogen receptor-alpha (ERalpha) can induce the expression of genes in response to estrogen by binding to estrogen response elements in the promoters of target genes. There is growing evidence that ERalpha can alter patterns of gene expression in response to ligand by regulating the activity of other factors through a ... More
Transcriptional repression of the anti-apoptotic survivin gene by wild type p53.
Authors Hoffman William H; Biade Siham; Zilfou Jack T; Chen Jiandong; Murphy Maureen;
JournalJ Biol Chem
PubMed ID11714700
'Survivin is a member of the inhibitor of apoptosis family. This apoptosis inhibitor also has an evolutionarily conserved role as a mitotic spindle checkpoint protein. Previous studies on p53-repressed genes have implicated several genes involved in the G(2)/M transition of the cell cycle as targets of negative regulation by p53. ... More
Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32).
AuthorsZhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW
JournalNature Genetics
PubMed ID10319863
'Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve the gastrointestinal tract and are the most common subset of extranodal non-Hodgkin lymphoma (NHL). Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to the recurrent t(1;14)(p22;q32). BCL10 ... More
Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14.
AuthorsAmes RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, Foley JJ, Sauermelch CF, Coatney RW, Ao Z, Disa J, Holmes SD, Stadel JM, Martin JD, Liu WS, Glover GI, Wilson S, McNulty DE, Ellis CE, Elshourbagy NA, Shabon U, Trill JJ, Hay DW, Douglas SA, et al
JournalNature
PubMed ID10499587
'Urotensin-II (U-II) is a vasoactive ''somatostatin-like'' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominantly in cardiovascular tissue, which functions as a U-II ... More
A strategy for rapid cDNA cloning from double-stranded RNA templates isolated from plants infected with RNA viruses by using DNA polymerase
AuthorsZhang YP, Rowhani A
JournalJ Virol Methods
PubMed ID10644087
'A fast and efficient cDNA cloning procedure for plant RNA viruses was developed. In this procedure, double-stranded RNA (dsRNA) was used as a template source. Standard cDNA synthesis reagents and random hexamers were then used for making cDNAs. Taq DNA polymerase was used to add additional (A) at the ends ... More
Site-directed Glycosylation Tagging of Functional Kir2.1 Reveals That the Putative Pore-forming Segment Is Extracellular.
'Inwardly rectifying K(+) channels or Kirs are a large gene family and have been predicted to have two transmembrane segments, M1 and M2, intracellular N and C termini, and two extracellular loops, E1 and E2, separated by an intramembranous pore-forming segment, H5. H5 contains a stretch of eight residues that ... More
The promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines is primarily localized to sequences in the amino-terminal domain.
Authors Lu Z H; Wang Z X; Horuk R; Hesselgesser J; Lou Y C; Hadley T J; Peiper S C;
JournalJournal of Biological Chemistry
PubMed ID7592830
'The Duffy antigen (DARC) is a promiscuous chemokine receptor that also binds Plasmodium vivax. DARC belongs to a family of heptahelical chemokine receptors that includes specific (IL-8RA) and shared (IL-8RB) IL-8 receptors. Ligand binding specificity of IL-8 receptors was localized to the amino-terminal extracellular (E1) domain. To determine the basis ... More
An N-terminal arginine-rich cluster and a proline-alanine-threonine repeat region determine the cellular localization of the herpes simplex virus type 1 ICP34.5 protein and its ligand, protein phosphatase 1.
Authors Mao Hanwen; Rosenthal Kenneth S;
JournalJ Biol Chem
PubMed ID11788604
'The ICP34.5 protein facilitates herpes simplex virus replication by binding and activating protein phosphatase 1 (PP1) by means of a very conserved C-terminal GADD34-like region. Natural variants of the ICP34.5 differing in the number of arginines in an Arg-rich cluster at the N terminus and the number of Pro-Ala-Thr repeats ... More
Evaluation of transgenic tomato plants expressing an additional phytoene synthase in a fruit-specific manner.
Authors Fraser Paul D; Romer Susanne; Shipton Cathie A; Mills Philippa B; Kiano Joy W; Misawa Norihiko; Drake Rachel G; Schuch Wolfgang; Bramley Peter M;
JournalProc Natl Acad Sci U S A
PubMed ID11805345
'Phytoene synthase from the bacterium Erwinia uredovora (crtB) has been overexpressed in tomato (Lycopersicon esculentum Mill. cv. Ailsa Craig). Fruit-specific expression was achieved by using the tomato polygalacturonase promoter, and the CRTB protein was targeted to the chromoplast by the tomato phytoene synthase-1 transit sequence. Total fruit carotenoids of primary ... More
Genetic Analysis of nif Regulatory Genes by Utilizing the Yeast Two-Hybrid System Detected Formation of a NifL-NifA Complex That Is Implicated in Regulated Expression of nif Genes.
AuthorsLei S, Pulakat L, Gavini N
JournalJ Bacteriol
PubMed ID10515947
'In diazotrophic organisms, nitrogenase synthesis and activity are tightly regulated. Two genes, nifL andnifA, are implicated as playing a major role in this regulation. NifA is a transcriptional activator, and itsactivity is inhibited by NifL in response to availability of excess fixed nitrogen and high O(2) tension. Itwas postulated that ... More
Quantitative Assessment of Gene Targeting in Vitro and in Vivo by the Pancreatic Transcription Factor, Pdx1. IMPORTANCE OF CHROMATIN STRUCTURE IN DIRECTING PROMOTER BINDING.
Authors Chakrabarti Swarup K; James Joshua C; Mirmira Raghavendra G;
JournalJ Biol Chem
PubMed ID11825903
'The transcription factor Pdx1 is expressed in the pancreatic beta-cell, where it is believed to regulate several beta-cell-specific genes. Whereas binding by Pdx1 to elements of beta-cell genes has been demonstrated in vitro, almost none of these genes has been demonstrated to be a direct binding target for Pdx1 within ... More
Substrate nucleotide-determined non-templated addition of adenine by Taq DNA polymerase: implications for PCR-based genotyping and cloning
'The Applied Biosystems PRISM fluorescence-based genotyping system as well as the Invitrogen TA Cloning vector system are influenced by the tendency of Taq DNA polymerase to add an adenine nucleotide to the 3'' end of PCR products after extension. Incomplete addition of adenine to a majority of PCR product strands ... More
The metal-binding properties of DREAM: evidence for calcium-mediated changes in DREAM structure.
Authors Craig Theodore A; Benson Linda M; Venyaminov Sergei Yu; Klimtchuk Elena S; Bajzer Zeljko; Prendergast Franklyn G; Naylor Stephen; Kumar Rajiv;
JournalJ Biol Chem
PubMed ID11788589
'DREAM, an EF-hand protein, associates with and modulates the activity of presenilins and Kv4 potassium channels in neural and cardiac tissues and represses prodynorphin and c-fos gene expression by binding to DNA response elements in these genes. Information concerning the metal-binding properties of DREAM and the consequences of metal binding ... More
The Role of Constant Region Carbohydrate in the Assembly and Secretion of Human IgD and IgA1.
Authors Gala Francoise A; Morrison Sherie L;
JournalJ Biol Chem
PubMed ID12023968
'Immunoglobulins are glycoproteins, containing N- linked carbohydrates in the heavy chain constant regions of all isotypes and O-linked carbohydrates in the hinge regions of human IgA1 and IgD. A previous study showed that IgD synthesized in the presence of tunicamycin and lacking the three N-linked glycans on the heavy chain ... More
Cytosine methylation and mammalian development.
AuthorsWalsh CP, Bestor TH
JournalGenes Dev
PubMed ID9887097
'Programmed methylation and demethylation of regulatory sequences has been proposed to play a central role in vertebrate development. We report here that the methylation status of the 5'' regions of a panel of tissue-specific genes could not be correlated with expression in tissues of fetal and newborn mice. Genes reported ... More
Reduction of false positives in prokaryotic mRNA differential display [In Process Citation]
AuthorsNagel A, Fleming JT, Sayler GS
JournalBiotechniques
PubMed ID10343902
TRPC4 Can Be Activated by G-protein-coupled Receptors and Provides Sufficient Ca2+ to Trigger Exocytosis in Neuroendocrine Cells.
Authors Obukhov Alexander G; Nowycky Martha C;
JournalJ Biol Chem
PubMed ID11856742
Transient receptor potential (TRP) channels form a large family of plasma membrane cation channels. Mammalian members of the
The plug domain of FepA, a TonB-dependent transport protein from Escherichia coli, binds its siderophore in the absence of the transmembrane barrel domain.
Authors Usher K C; Ozkan E; Gardner K H; Deisenhofer J;
JournalProc Natl Acad Sci U S A
PubMed ID11526207
FepA, an outer membrane iron siderophore transporter from Escherichia coli, is composed of a 22-stranded membrane-spanning beta barrel with a globular N-terminal
Cloning of mammalian heparanase, an important enzyme in tumor invasionand metastasis.
The endoglycosidase heparanase is an important in the degradation of the extracellular matrix by invading cells, notably metastatic tumor cells and migrating leukocytes. Here we report the cDNA sequence of the human platelet enzyme, which encodes a unique protein of 543 amino acids, and the identification of highly homologous sequences ... More
Molecular characterization of the starfish inositol 1,4,5-trisphosphate receptor and its role during oocyte maturation and fertilization.
The release of calcium ions (Ca(2+)) from their intracellular stores is essential for the fertilization of oocytes of various species. The calcium pools can be induced to release Ca(2+) via two main types of calcium channel receptor: the inositol 1,4,5-trisphosphate receptor (IP(3)R) and the ryanodine receptor. Starfish oocytes have often ... More
AUF1 Is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis.
We previously identified a conserved A + U-rich element (ARE) in the 3'-untranslated region of bcl-2 mRNA. We have also recently demonstrated that the bcl-2 ARE interacts with a number of ARE-binding proteins (AUBPs) whose pattern changes during apoptosis in association with bcl-2 mRNA half-life reduction. Here we show that ... More
6S RNA regulates E. coli RNA polymerase activity.
AuthorsWassarman KM, Storz G
JournalCell
PubMed ID10892648
The E. coli 6S RNA was discovered more than three decades ago, yet its function has remained elusive. Here, we demonstrate that 6S RNA associates with RNA polymerase in a highly specific and efficient manner. UV crosslinking experiments revealed that 6S RNA directly contacts the sigma70 and beta/beta' subunits ... More
Cloning PCR products with T-vectors.
AuthorsNichols WA,
JournalMethods Mol Biol
PubMed ID12904657
Since it was described in 1988, the polymerase chain reaction (PCR) has been a valuable tool for molecular biologists. PCR allows researchers to produce a large quantity of a desired DNA fragment while requiring only a small amount of template. Prior to PCR, isolation of DNA fragments was typically performed ... More
Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase.
AuthorsHuang JT, Welch JS, Ricote M, Binder CJ, Willson TM, Kelly C, Witztum JL, Funk CD, Conrad D, Glass CK
JournalNature
PubMed ID10432118
The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent nuclear receptor that has been implicated in the modulation of critical aspects of development and homeostasis, including adipocyte differentiation, glucose metabolism and macrophage development and function. PPAR-gamma is activated by a range of synthetic and naturally occurring substances, including antidiabetic thiazolidinediones, polyunsaturated ... More
A protein phosphatase functions to recycle RNA polymerase II [In Process Citation]
AuthorsCho H, Kim TK, Mancebo H, Lane WS, Flores O, Reinberg D
JournalGenes Dev
PubMed ID10385623
Transcription is regulated by the state of phosphorylation of a heptapeptide repeat known as the carboxy-terminal domain (CTD) present in the largest subunit of RNA polymerase II (RNAPII). RNAPII that associates with transcription initiation complexes contains an unphosphorylated CTD, whereas the elongating polymerase has a phosphorylated CTD. Transcription factor IIH ... More
Characterization of otoconin-95, the major protein of murine otoconia, provides insights into the formation of these inner ear biominerals.
AuthorsVerpy E, Leibovici M, Petit C
JournalProc Natl Acad Sci U S A
PubMed ID9892667
During the course of a study aimed at identifying inner ear-specific transcripts, a 1,906-bp murine cDNA predicted to encode a secreted 469- aa protein with two domains of homology with the secreted phospholipases A2 was isolated. This transcript is specifically expressed in the inner ear from embryonic day 9.5. The ... More
Molecular cloning and functional expression of gibberellin 2- oxidases, multifunctional enzymes involved in gibberellin deactivation.
AuthorsThomas SG, Phillips AL, Hedden P
JournalProc Natl Acad Sci U S A
PubMed ID10200325
A major catabolic pathway for the gibberellins (GAs) is initiated by 2beta-hydroxylation, a reaction catalyzed by 2-oxoglutarate-dependent dioxygenases. To isolate a GA 2beta-hydroxylase cDNA clone we used functional screening of a cDNA library from developing cotyledons of runner bean (Phaseolus coccineus L.) with a highly sensitive tritium- release assay for ... More
RAG-2 promotes heptamer occupancy by RAG-1 in the assembly of a V(D)J initiation complex.
AuthorsSwanson PC, Desiderio S
JournalMol Cell Biol
PubMed ID10207091
V(D)J recombination occurs at recombination signal sequences (RSSs) containing conserved heptamer and nonamer elements. RAG-1 and RAG-2 initiate recombination by cleaving DNA between heptamers and antigen receptor coding segments. RAG-1 alone contacts the nonamer but interacts weakly, if at all, with the heptamer. RAG-2 by itself has no DNA-binding activity ... More
Vascular endothelial growth factor activates nuclear factor of activated T cells in human endothelial cells: a role for tissue factor gene expression.
AuthorsArmesilla AL, Lorenzo E, Gomez del Arco P, Martinez-Martinez S, Alfranca A, Redondo JM
JournalMol Biochem Parasitol
PubMed ID10022890
Vascular endothelial growth factor (VEGF) is a potent angiogenic inducer that stimulates the expression of tissue factor (TF), the major cellular initiator of blood coagulation. Here we show that signaling triggered by VEGF induced DNA-binding and transcriptional activities of nuclear factor of activated T cells (NFAT) and AP-1 in human ... More
Atrial natriuretic peptide-stimulated Ca2+ reabsorption in rabbit kidney requires membrane-targeted, cGMP-dependent protein kinase type II.
AuthorsHoenderop JG, Vaandrager AB, Dijkink L, Smolenski A, Gambaryan S, Lohmann SM, de Jonge HR, Willems PH, Bindels RJ
JournalProc Natl Acad Sci U S A
PubMed ID10339545
Atrial natriuretic peptide (ANP) and nitric oxide (NO) are key regulators of ion and water transport in the kidney. Here, we report that these cGMP-elevating hormones stimulate Ca2+ reabsorption via a novel mechanism specifically involving type II cGMP-dependent protein kinase (cGK II). ANP and the NO donor, sodium nitroprusside (SNP), ... More
Characterization of two chloroplast RNA polymerase sigma factors from Zea mays: photoregulation and differential expression.
AuthorsTan S, Troxler RF
JournalProc Natl Acad Sci U S A
PubMed ID10220463
Two distinct cDNAs encoding putative sigma factors of plastid RNA polymerase were isolated from Zea mays, a C4 plant. The deduced amino acid sequences of both cDNAs possess all four highly conserved domains proposed for recognition of -10 and -35 promoter elements, core complex binding, DNA binding, and melting. These ... More
T cell receptor V alpha 4 is expressed by a subpopulation of V beta 6 T cells that respond to the bacterial superantigen staphylococcal enterotoxin B.
AuthorsBorrero H, Donson D, Cervera C, Rexer C, Macphail S
JournalJ Immunol
PubMed ID7722285
A subpopulation of murine minor lymphocyte-stimulating locus Ag (Mls)- 1a-responsive, TCR V beta 6-expressing T hybrids was responsive to the superantigenic bacterial toxin, staphylococcal enterotoxin B (SEB), presented by murine MHC class II molecules. Comparative functional and surface marker analyses showed that this heterogeneity was not caused by nonspecific effects. ... More
Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytes/macrophages.
AuthorsRadolf JD, Arndt LL, Akins DR, Curetty LL, Levi ME, Shen Y, Davis LS, Norgard MV
JournalJ Immunol
PubMed ID7876555
The observation that the major membrane immunogens of the spirochetal pathogens. Treponema pallidum and Borrelia burgdorferi are lipoproteins prompted studies to investigate macrophage activation by the 47-kDa lipoprotein of T. pallidum and the acylated outer surface protein A (OspA) of B. burgdorferi. Both lipoproteins induced the synthesis of biologically active ... More
Missense mutations in desmin associated with familial cardiac and skeletal myopathy.
AuthorsGoldfarb LG, Park KY, Cervenakova L, Gorokhova S, Lee HS, Vasconcelos O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC
JournalNature Genetics
PubMed ID9697706
Desmin-related myopathy (OMIM 601419) is a familial disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. The underlying molecular mechanisms are unknown. Involvement of the desmin gene (DES) has been ... More
Molecular analysis of a novel winged helix protein, WIN. Expression pattern, DNA binding property, and alternative splicing within the DNA binding domain.
AuthorsYao KM, Sha M, Lu Z, Wong GG
JournalJ Biol Chem
PubMed ID9242644
We have cloned a novel winged helix factor, WIN, from the rat insulinoma cell line, INS-1. Northern blot analysis demonstrated that WIN is highly expressed in a variety of insulinoma cell lines and rat embryonic pancreas and liver. In adults, WIN expression was detected in thymus, testis, lung, and several ... More
Yeast flavin-containing monooxygenase is induced by the unfolded protein response.
AuthorsSuh JK, Robertus JD
JournalProc Natl Acad Sci
PubMed ID10618381
Flavin-containing monooxygenase from yeast (yFMO) carries out the O(2)- and NADPH-dependent oxidation of biological thiols, including oxidizing glutathione to glutathione disulfide. FMO provides a large fraction of the oxidizing necessary for proper folding of disulfide bond-containing proteins; deletion of the enzyme reduces proper folding of endogenous carboxypeptidase Y by about ... More
Dual targeting of spinach protoporphyrinogen oxidase II to mitochondria and chloroplasts by alternative use of two in-frame initiation codons.
Authors Watanabe N; Che F S; Iwano M; Takayama S; Yoshida S; Isogai A;
JournalJ Biol Chem
PubMed ID11274159
Protoporphyrinogen oxidase (Protox) is the final enzyme in the common pathway of chlorophyll and heme biosynthesis. Two Protox isoenzymes have been described in tobacco, a plastidic and a mitochondrial form. We isolated and sequenced spinach Protox cDNA, which encodes a homolog of tobacco mitochondrial Protox (Protox II). Alignment of the ... More
Sequence evolution and copy number of Ty1-copia retrotransposons in diverse plant genomes.
Authors Navarro-Quezada Aura; Schoen Daniel J;
JournalProc Natl Acad Sci U S A
PubMed ID11752395
Sequence evolution of the reverse transcriptase (RT) gene in retrotransposons belonging to the Ty1-copia class was studied in 11 plant species. Phylogenetic reconstruction of the evolutionary history of RT sequences indicated a strong pattern of purifying selection, manifested as high ratios of third to first plus second codon position substitutions, ... More
Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF): a mechanism contributing to VEGF-induced angiogenesis.
Neuropilin (NRP) 1, previously identified as a neuronal receptor that mediates repulsive growth cone guidance, has been shown recently to function also in endothelial cells as an isoform-specific receptor for vascular endothelial growth factor (VEGF)(165) and as a coreceptor in vitro of VEGF receptor 2. However, its potential role in ... More
The N-terminal SH2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin beta cytoplasmic domains.
AuthorsWoodside DG, Obergfell A, Talapatra A, Calderwood DA, Shattil SJ, Ginsberg MH
JournalJ Biol Chem
PubMed ID12171941
Syk and ZAP-70 form a subfamily of nonreceptor tyrosine kinases that contain tandem SH2 domains at their N termini. Engagement of these SH2 domains by tyrosine-phosphorylated immunoreceptor tyrosine-based activation motifs leads to kinase activation and downstream signaling. These kinases are also regulated by beta3 integrin-dependent cell adhesion via a phosphorylation-independent ... More
Plunc, a member of the secretory gland protein family, is up-regulated in nasal respiratory epithelium after olfactory bulbectomy.
Subtraction suppression hybridization was used with high throughput screening to identify transcripts of genes that are differentially expressed in nasal epithelium following lesioning of the olfactory bulb, termed bulbectomy. We isolated the rat homologue of plunc, a murine gene highly expressed in lung and nasopharyngeal regions, by this method. Rat ... More
The oncoprotein Set/TAF-1beta, an inhibitor of histone acetyltransferase, inhibits active demethylation of DNA, integrating DNA methylation and transcriptional silencing.
Histone hypoacetylation and DNA hypermethylation are hallmarks of gene silencing. Although a role for DNA methylation in regulating histone acetylation has been established, it is not clear how and whether epigenetic histone markings influence DNA modifications in transcriptional silencing. We have previously shown that induction of histone acetylation by trichostatin ... More
Regulation of the Epithelial Sodium Channel by Serine Proteases in Human Airways.
Authors Donaldson Scott H.; Hirsh Andrew; Li Dong Chen; Holloway Ginger; Chao Julie; Boucher Richard C.; Gabriel Sherif E.;
JournalJ Biol Chem
PubMed ID11756432
The epithelial sodium channel (ENaC) constitutes the rate-limiting step for sodium absorption across airway epithelia, which in turn regulates airway surface liquid (ASL) volume and the efficiency of mucociliary clearance. This role in ASL volume regulation suggests that ENaC activity is influenced by local factors rather than systemic signals indicative ... More
High glucose-altered gene expression in mesangial cells. Actin-regulatory protein gene expression is triggered by oxidative stress and cytoskeletal disassembly.
Authors Clarkson Michael R; Murphy Madeline; Gupta Sunil; Lambe Teresa; Mackenzie Harald S; Godson Catherine; Martin Finian; Brady Hugh R;
JournalJ Biol Chem
PubMed ID11784718
High extracellular glucose plays a pivotal role in the pathophysiology of diabetic nephropathy. Here we report 200 genes, identified using suppression-subtractive hybridization, that are differentially expressed when human mesangial cells are propagated in high ambient glucose in vitro. The major functional classes of genes identified included modulators and products of ... More
Barbiturase, a novel zinc-containing amidohydrolase involved in oxidative pyrimidine metabolism.
Barbiturase, which catalyzes the reversible amidohydrolysis of barbituric acid to ureidomalonic acid in the second step of oxidative pyrimidine degradation, was purified to homogeneity from Rhodococcus erythropolis JCM 3132. The characteristics and gene organization of barbiturase suggested that it is a novel zinc-containing amidohydrolase that should be grouped into a ... More
Lateral transfer at the gene and subgenic levels in the evolution of eukaryotic enolase.
Authors Keeling P J; Palmer J D;
JournalProc Natl Acad Sci U S A
PubMed ID11526220
Enolase genes from land plants and apicomplexa (intracellular parasites, including the malarial parasite, Plasmodium) share two short insertions. This observation has led to the suggestion that the apicomplexan enolase is the product of a lateral transfer event involving the algal endosymbiont from which the apicomplexan plastid is derived. We have ... More
Alterations in the sensing and transport of phosphate and calcium by differentiating chondrocytes.
Authors Wang D; Canaff L; Davidson D; Corluka A; Liu H; Hendy G N; Henderson J E;
JournalJ Biol Chem
PubMed ID11404353
During endochondral bone formation and fracture healing, cells committed to chondrogenesis undergo a temporally restricted program of differentiation that is characterized by sequential changes in their phenotype and gene expression. This results in the manufacture, remodeling, and mineralization of a cartilage template on which bone is laid down. Articular chondrocytes ... More
Membrane localization of 3-phosphoinositide-dependent protein kinase-1 stimulates activities of Akt and atypical protein kinase C but does not stimulate glucose transport and glycogen synthesis in 3T3-L1 adipocytes.
AuthorsEgawa K, Maegawa H, Shi K, Nakamura T, Obata T, Yoshizaki T, Morino K, Shimizu S, Nishio Y, Suzuki E, Kashiwagi A.
JournalJ Biol Chem
PubMed ID12147684
It is reported that 3-phosphoinositide-dependent protein kinase-1 (PDK-1) is activated in a phosphatidylinositol 3,4,5-trisphosphate-dependent manner and phosphorylates Akt, p70S6 kinase, and atypical protein kinase C (PKC), but its function on insulin signaling is still unclear. We cloned a full-length pdk-1 cDNA from a human brain cDNA library, and the adenovirus ... More
Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen.
Authors Wei Y Q; Huang M J; Yang L; Zhao X; Tian L; Lu Y; Shu J M; Lu C J; Niu T; Kang B; Mao Y Q; Liu F; Wen Y J; Lei S; Luo F; Zhou L Q; Peng F; Jiang Y; Liu J Y; Zhou H; Wang Q R; He Q M; Xiao F; Lou Y Y; Xie X J; Li Q; Wu Y; Ding Z Y; Hu B; Hu M; Zhang W;
JournalProc Natl Acad Sci U S A
PubMed ID11553767
Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic ... More
Characterization of the murine hyaluronidase gene region reveals complex organization and cotranscription of Hyal1 with downstream genes, Fus2 and Hyal3.
Authors Shuttleworth Tamara L; Wilson Michael D; Wicklow Brandy A; Wilkins John A; Triggs-Raine Barbara L;
JournalJ Biol Chem
PubMed ID11929860
Hyaluronidases are required for the breakdown of hyaluronan (HA), an abundant component of the extracellular matrix of vertebrate tissues. Multiple hyaluronidase genes have been identified, but the only clue to the function of their products has come from the identification of hyaluronidase 1 deficiency in a single patient with a ... More
Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis.
DNA hypomethylation on pericentromeric satellite regions is an early and frequent event associated with heterochromatin instability during human hepatocarcinogenesis. A DNA methyltransferase, DNMT3b, is required for methylation on pericentromeric satellite regions during mouse development. To clarify the molecular mechanism underlying DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis, we ... More
Promoter-specific Activation and Demethylation by MBD2/Demethylase.
MBD2 is the only member of a family of methyl-CpG-binding proteins that has been reported to be both a transcriptional repressor and a DNA demethylase (dMTase). To understand the apparently contradictory function of MBD2/dMTase, we studied the effects of dMTase overexpression on the activity of various in vitro methylated promoters ... More
Splitting the two pore domains from TOK1 results in two cationic channels with novel functional properties.
Potassium channels are membrane-spanning proteins with several transmembrane segments and a single pore region where ion conduction takes place (Biggin, P. C., Roosild, T., and Choe, S. (2000) Curr. Opin. Struct. Biol. 4, 456-461; Doyle, D. A., Morais Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. ... More