Rapamycin has been shown to affect translation. We have utilized two complementary approaches to identify genes that are predominantly affected by rapamycin in Jurkat T cells. One was to compare levels of polysome-bound and total RNA using oligonucleotide microarrays complementary to 6,300 human genes. Another was to determine protein synthesis ... More
STARS, a Striated Muscle Activator of Rho Signaling and Serum Response Factor-dependent Transcription.
Authors Arai Akiko; Spencer Jeffrey A; Olson Eric N;
JournalJ Biol Chem
PubMed ID11983702
'Changes in actin dynamics influence diverse cellular processes and couple the actin-based cytoskeleton to changes in gene transcription. Members of the Rho GTPase family regulate cytoskeletal organization by stimulating actin polymerization and stress fiber formation when activated by extracellular signaling. The transcriptional activity of serum response factor (SRF) is stimulated ... More
Transcriptional effects of chronic Akt activation in the heart.
Authors Cook Stuart A; Matsui Takashi; Li Ling; Rosenzweig Anthony;
JournalJ Biol Chem
PubMed ID11956204
'Akt activation reduces cardiomyocyte death and induces cardiac hypertrophy. To help identify effector mechanisms, gene expression profiles in hearts from transgenic mice with cardiac-specific expression of activated Akt (myr-Akt) were compared with littermate controls. 40 genes were identified as differentially expressed. Quantitative reverse transcription-PCR confirmed qualitative results of transcript profiling ... More
Regulation of mRNA expression in macrophages after Yersinia enterocolitica infection. Role of different Yop effectors.
'The Yop virulon, which comprises a complete type III secretion system and secreted proteins, allows bacteria from the genus Yersinia to resist the nonspecific immune response of the host. This virulon, which is encoded by a plasmid called pYV in Yersinia enterocolitica, enables extracellular bacteria to inject six Yop effectors ... More
Fragmin60 encodes an actin-binding protein with a C2 domain and controls actin Thr-203 phosphorylation in Physarum plasmodia and sclerotia.
AuthorsSklyarova T, De Corte V, Meerschaert K, Devriendt L, Vanloo B, Bailey J, Cook LJ, Goethals M, Van Damme J, Puype M, Vandekerckhove J, Gettemans J.
JournalJ Biol Chem
PubMed ID12167630
'We report the isolation of a cDNA clone encoding a 60-kDa protein termed fragmin60 that cross-reacts with fragmin antibodies. Unlike other gelsolin-related proteins, fragmin60 contains a unique N-terminal domain that shows similarity with C2 domains of aczonin, protein kinase C, and synaptotagmins. The fragmin60 C2 domain binds three calcium ions, ... More
Mediation by a CREB Family Transcription Factor of NGF-Dependent Survival of Sympathetic Neurons
AuthorsAntonella Riccio, 1 Sohyun Ahn, 1 Christopher M. Davenport, 1 Julie A. Blendy, 2 David D. Ginty 1*
JournalScience
PubMed ID10600750
'Nerve growth factor (NGF) and other neurotrophins support survival of neurons through processes that are incompletely understood. The transcription factor CREB is a critical mediator ofNGF-dependent gene expression, but whether CREB family transcription factors regulate expression of genes that contribute to NGF-dependent survival of sympathetic neurons is unknown. CREB-mediated gene ... More
Effects of hydrogen bonding within a damaged base pair on the activity of wild type and DNA-intercalating mutants of human alkyladenine DNA glycosylase.
Authors Vallur Aarthy C; Feller Joyce A; Abner Clint W; Tran Robert K; Bloom Linda B;
JournalJ Biol Chem
PubMed ID12077143
'Human alkyladenine DNA glycosylase '
Regulation of stress response signaling by the N-terminal dishevelled/EGL-10/pleckstrin domain of Sst2, a regulator of G protein signaling in Saccharomyces cerevisiae.
Authors Burchett Scott A; Flanary Paul; Aston Christopher; Jiang Lixin; Young Kathleen H; Uetz Peter; Fields Stanley; Dohlman Henrik G;
JournalJ Biol Chem
PubMed ID11940600
'All members of the regulator of G protein signaling (RGS) family contain a conserved core domain that can accelerate G protein GTPase activity. The RGS in yeast, Sst2, can inhibit a G protein signal leading to mating. In addition, some RGS proteins contain an N-terminal domain of unknown function. Here ... More
Interaction of intracellular beta amyloid peptide with chaperone proteins.
Authors Fonte Virginia; Kapulkin Vadim; Taft Andrew; Fluet Amy; Friedman David; Link Christopher D;
JournalProc Natl Acad Sci U S A
PubMed ID12089340
'Expression of the human beta amyloid peptide (A beta) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular A beta in vivo. Mass spectrometry analysis ... More
Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: Evidence from high-density oligonucleotide arrays and in situ hybridization.
AuthorsMong JA, Devidze N, Frail DE, O'Connor LT, Samuel M, Choleris E, Ogawa S, Pfaff DW,
JournalProc Natl Acad Sci U S A
PubMed ID12518068
'Microarrays comprise an efficient approach to discovering large numbers of differentially expressed mRNA transcripts in the CNS resulting from changes in hormonal milieu. We used high-density oligonucleotide microarrays to examine the short- and long-term actions of estradiol (E(2)) on the transcriptomes from the medial basal hypothalamus and other brain regions ... More
Identification of a gene encoding MGAT1, a monoacylglycerol acyltransferase.
Authors Yen Chi-Liang Eric; Stone Scot J; Cases Sylvaine; Zhou Ping; Farese Robert V Jr;
JournalProc Natl Acad Sci U S A
PubMed ID12077311
'Acyl-CoA:monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol, the precursor of physiologically important lipids such as triacylglycerol and phospholipids. In the intestine, MGAT plays a major role in the absorption of dietary fat because resynthesis of triacylglycerol is required for the assembly of lipoproteins that transport absorbed fat to other ... More
Slug is a novel downstream target of MyoD. Temporal profiling in muscle regeneration.
'Temporal expression profiling was utilized to define transcriptional regulatory pathways in vivo in a mouse muscle regeneration model. Potential downstream targets of MyoD were identified by temporal expression, promoter data base mining, and gel shift assays; Slug and calpain 6 were identified as novel MyoD targets. Slug, a member of ... More
Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes.
AuthorsNguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, Pittelkow M, Grando SA,
JournalJ Biol Chem
PubMed ID14600150
Pemphigus vulgaris (PV) is a life-threatening autoimmune disease of skin adhesion associated with IgG autoantibodies against keratinocytes (KC). Treatment of PV with systemic corticosteroids is life-saving, but the mechanism of the therapeutic action has not been fully understood. We have developed an animal model that demonstrates that methylprednisolone (MP) can ... More
A novel membrane protein, Ros3p, is required for phospholipid translocation across the plasma membrane in Saccharomyces cerevisiae.
AuthorsKato U, Emoto K, Fredriksson C, Nakamura H, Ohta A, Kobayashi T, Murakami-Murofushi K, Kobayashi T, Umeda M,
JournalJ Biol Chem
PubMed ID12133835
Ro09-0198 (Ro) is a tetracyclic peptide antibiotic that binds specifically to phosphatidylethanolamine (PE) and causes cytolysis. To investigate the molecular basis of transbilayer movement of PE in biological membranes, we have isolated a series of budding yeast mutants that are hypersensitive to the Ro peptide. One of the most sensitive ... More
Mitochondrial and cytoplasmic thioredoxin reductase variants encoded by a single Drosophila gene are both essential for viability.
Authors Missirlis Fanis; Ulschmid Julia K; Hirosawa-Takamori Mitsuko; Grönke Sebastian; Schäfer Ulrich; Becker Katja; Phillips John P; Jäckle Herbert;
JournalJ Biol Chem
PubMed ID11796729
Defense against oxidative stress in mammals includes the regeneration of the major thiol reductants glutathione and thioredoxin by glutathione reductase and thioredoxin reductase (TrxR), respectively. In contrast, Drosophila, and possibly insects in general, lacks glutathione reductase and must rely solely on the TrxR system. The mammalian TrxRs described so far ... More
PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice.
Authors Zinker Bradley A; Rondinone Cristina M; Trevillyan James M; Gum Rebecca J; Clampit Jill E; Waring Jeffrey F; Xie Nancy; Wilcox Denise; Jacobson Peer; Frost Leigh; Kroeger Paul E; Reilly Regina M; Koterski Sandra; Opgenorth Terry J; Ulrich Roger G; Crosby Seth; Butler Madeline; Murray Susan F; McKay Robert A; Bhanot Sanjay; Monia Brett P; Jirousek Michael R;
JournalProc Natl Acad Sci U S A
PubMed ID12169659
The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA(1C). Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and ... More
HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication.
Authors Cicala Claudia; Arthos James; Selig Sara M; Dennis Glynn Jr; Hosack Douglas A; Van Ryk Donald; Spangler Marion L; Steenbeke Tavis D; Khazanie Prateeti; Gupta Neil; Yang Jun; Daucher Marybeth; Lempicki Richard A; Fauci Anthony S;
JournalProc Natl Acad Sci U S A
PubMed ID12089333
Certain HIV-encoded proteins modify host-cell gene expression in a manner that facilitates viral replication. These activities may contribute to low-level viral replication in nonproliferating cells. Through the use of oligonucleotide microarrays and high-throughput Western blotting we demonstrate that one of these proteins, gp120, induces the expression of cytokines, chemokines, kinases, ... More
A new functional screening system for identification of regulators for the generation of amyloid beta-protein.
AuthorsKomano H, Shiraishi H, Kawamura Y, Sai X, Suzuki R, Serneels L, Kawaichi M, Kitamura T, Yanagisawa K.
JournalJ Biol Chem
PubMed ID12161439
Presenilin (PS) is essential for gamma-cleavage, which is required for the generation of amyloid beta-protein (Abeta) from the beta-amyloid precursor protein. However, it remains to be clarified how gamma-cleavage is regulated. To elucidate the regulation of PS-mediated gamma-cleavage, we developed a new functional screening method for identifying cDNA that enhances ... More
Food deprivation-induced expression of minoxidil sulfotransferase in the hypothalamus uncovered by microarray analysis.
Authors Li Ji-Yao; Lescure Pascal A; Misek David E; Lai Yu-Mei; Chai Biao-Xin; Kuick Rork; Thompson Robert C; Demo Rebecca M; Kurnit David M; Michailidis George; Hanash Samir M; Gantz Ira;
JournalJ Biol Chem
PubMed ID11782476
We used oligonucleotide microarrays to analyze comprehensively hypothalamic gene expression changes that correlate with energy homeostasis. We compared the hypothalamic gene expression profiles of freely fed and 48-h fasted rats using 26,379 oligonucleotide probe sets. Expression of 96 genes was up-regulated and expression of 73 genes was down-regulated in a ... More
Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast.
Authors Wilcox Lisa J; Balderes Dina A; Wharton Brook; Tinkelenberg Arthur H; Rao Govinda; Sturley Stephen L;
JournalJ Biol Chem
PubMed ID12077145
In contrast to lipoprotein-mediated sterol uptake, free sterol influx by eukaryotic cells is poorly understood. To identify components of non-lipoprotein-mediated sterol uptake, we utilized strains of Saccharomyces cerevisiae that accumulate exogenous sterol due to a neomorphic mutation in the transcription factor, UPC2. Two congenic upc2-1 strains, differing quantitatively in aerobic ... More
Blocking the secretion of hepatic very low density lipoproteins renders the liver more susceptible to toxin-induced injury.
Authors Björkegren Johan; Beigneux Anne; Bergo Martin O; Maher Jacquelyn J; Young Stephen G;
JournalJ Biol Chem
PubMed ID11739387
Recently, we generated mice lacking microsomal triglyceride transfer protein (MTP) in the liver (Mttp(Delta/Delta)) and demonstrated that very low density lipoprotein secretion from hepatocytes was almost completely blocked. The blockade in lipoprotein production was accompanied by mild to moderate hepatic steatosis, but the mice appeared healthy. Although hepatic MTP deficiency ... More
Loss of Transgelin in Breast and Colon Tumors and in RIE-1 Cells by Ras Deregulation of Gene Expression through Raf-independent Pathways.
Authors Shields Janiel M; Rogers-Graham Kelley; Der Channing J;
JournalJ Biol Chem
PubMed ID11773051
Activated Ras but not Raf can transform RIE-1 and other epithelial cells, indicating the critical importance of Raf-independent effector function in Ras transformation of epithelial cells. To elucidate the nature of these Raf-independent activities, we utilized representational difference analysis to identify genes aberrantly expressed by Ras through Raf-independent mechanisms in ... More