Inhibition of v-raf-dependent c-fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2.


:Receptor-bound growth factors elicit intracellular signals that lead to the phosphorylation and activation of numerous intracellular kinases and transcription factors with consequent changes in patterns of gene expression. Several oncogene products are able to mimic these signals, resulting in cell transformation and proliferation. For example, the introduction of oncogenic forms of Raf-1 kinase into fibroblasts induces transformation and leads to the constitutive expression of, among others, the c-fos proto-oncogene. Here it is shown that the elevation of c-fos promoter activity brought about by v-raf is mediated by TCF/Elk-1, which forms a ternary complex with SRF at the serum response element and is a substrate for mitogen-activating protein kinases in vitro. In NIH 3T3 fibroblasts, v-raf activates Erk2, and overexpression of an interfering mutant of Erk2 both blocks the ability of v-raf to activate the c-fos promoter and suppresses transformation. Mutation of individual mitogen-activating protein kinase phosphoacceptor sites in TCF/Elk-1 also compromises v-raf-activated expression of a Gal-Elk/Gal-chloramphenicol acetyltransferase reporter system. However, in at least one instance the introduction of glutamate, but not aspartate, at a phosphoacceptor site is compatible with activation. These results provide compelling evidence that phosphorylation of TCF/Elk-1 by Erk2 is a major link in the Raf-1 kinase-dependent signal transduction pathway that activates c-fos expression.


Mol Cell Biol


Kortenjann M,Thomae O,Shaw PE




Has Abstract


1994-07-01 00:00:00












  • TFIIA induces conformational changes in TFIID via interactions with the basic repeat.

    abstract::DNA-binding studies with Saccharomyces cerevisiae TFIID point mutants indicated that TFIIA interacts with the basic repeat region of TFIID and induces structural changes. The latter was shown by the ability of TFIIA to compensate for TFIID point mutants defective for DNA binding. Interaction with TFIIA also rendered T...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lee DK,DeJong J,Hashimoto S,Horikoshi M,Roeder RG

    更新日期:1992-11-01 00:00:00

  • Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis.

    abstract::Despite detailed knowledge of the components of the spindle assembly checkpoint, a molecular explanation of how cells die after prolonged spindle checkpoint activation, and thus how microtubule inhibitors and other antimitotic drugs ultimately elicit their lethal effects, has yet to emerge. Mitotically arrested cells ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Terrano DT,Upreti M,Chambers TC

    更新日期:2010-02-01 00:00:00

  • Structure of the chromosome VII centromere region in Neurospora crassa: degenerate transposons and simple repeats.

    abstract::DNA from the centromere region of linkage group (LG) VII of Neurospora crassa was cloned previously from a yeast artificial chromosome library and was found to be atypical of Neurospora DNA in both composition (AT rich) and complexity (repetitive). We have determined the DNA sequence of a small portion (approximately ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cambareri EB,Aisner R,Carbon J

    更新日期:1998-09-01 00:00:00

  • Modulation of transforming growth factor type beta action by activated ras and c-myc.

    abstract::Transfection of C3H/10T1/2 cells with a c-myc gene resulted in the acquisition of responsiveness to transforming growth factor type beta. Cells transfected with an activated H-ras gene or an H-ras and c-myc gene, however, exhibited a transformed morphology and spontaneous soft-agar growth, a phenotype induced reversib...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Leof EB,Proper JA,Moses HL

    更新日期:1987-07-01 00:00:00

  • DOT4 links silencing and cell growth in Saccharomyces cerevisiae.

    abstract::Transcriptional silencing in Saccharomyces cerevisiae occurs at specific loci and is mediated by a multiprotein complex that includes Rap1p and the Sir proteins. We studied the function of a recently identified gene, DOT4, that disrupts silencing when overexpressed. DOT4 encodes an ubiquitin processing protease (hydro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kahana A,Gottschling DE

    更新日期:1999-10-01 00:00:00

  • Aryl hydrocarbon receptor-mediated transcription: ligand-dependent recruitment of estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters.

    abstract::Using chromatin immunoprecipitation assays, we studied the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated recruitment of the aryl hydrocarbon receptor (AhR) and several co-regulators to the CYP1A1 promoter. AhR displayed a time-dependent recruitment, reaching a peak at 75 min and maintaining promoter occupancy fo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Matthews J,Wihlén B,Thomsen J,Gustafsson JA

    更新日期:2005-07-01 00:00:00

  • Internal ribosome entry site structural motifs conserved among mammalian fibroblast growth factor 1 alternatively spliced mRNAs.

    abstract::Fibroblast growth factor 1 (FGF-1) is a powerful angiogenic factor whose gene structure contains four promoters, giving rise to a process of alternative splicing resulting in four mRNAs with alternative 5' untranslated regions (5' UTRs). Here we have identified, by using double luciferase bicistronic vectors, the pres...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Martineau Y,Le Bec C,Monbrun L,Allo V,Chiu IM,Danos O,Moine H,Prats H,Prats AC

    更新日期:2004-09-01 00:00:00

  • Inverted duplication-transposition event in mammalian cells at an illegitimate recombination join.

    abstract::Illegitimate recombination events in mammalian cells often contain extraneous nucleotides or filler DNA at the recombinant joins. The polyomavirus-transformed cell line 7axB has previously been found to contain 37 base pairs (bp) of filler DNA at one virus-host join of the single insert of integrated viral DNA (A. Hay...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Williams TJ,Fried M

    更新日期:1986-06-01 00:00:00

  • Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor alpha gene promoter.

    abstract::The human tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated in response to multiple signals of stress and inflammation. We have identified transcription factors present in the TNF-alpha enhancer complex in vivo following ionophore stimulation (ATF-2/Jun and NFAT) and virus infection (ATF-2/Jun, NFAT, a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Falvo JV,Uglialoro AM,Brinkman BM,Merika M,Parekh BS,Tsai EY,King HC,Morielli AD,Peralta EG,Maniatis T,Thanos D,Goldfeld AE

    更新日期:2000-03-01 00:00:00

  • The notch intracellular domain can function as a coactivator for LEF-1.

    abstract::Notch signaling commences with two ligand-mediated proteolysis events that release the Notch intracellular domain, NICD, from the plasma membrane. NICD then translocates into the nucleus and interacts with the DNA binding protein CSL to activate transcription. We found that NICD expression also potentiates activity of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ross DA,Kadesch T

    更新日期:2001-11-01 00:00:00

  • Mutations in the yeast KEX2 gene cause a Vma(-)-like phenotype: a possible role for the Kex2 endoprotease in vacuolar acidification.

    abstract::Mutants of Saccharomyces cerevisiae that lack vacuolar proton-translocating ATPase (V-ATPase) activity show a well-defined set of Vma- (stands for vacuolar membrane ATPase activity) phenotypes that include pH-conditional growth, increased calcium sensitivity, and the inability to grow on nonfermentable carbon sources....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Oluwatosin YE,Kane PM

    更新日期:1998-03-01 00:00:00

  • Cholera toxin induces expression of the immediate-early response gene JE via a cyclic AMP-independent signaling pathway.

    abstract::Cholera toxin (CT) activates expression of two immediate-early response genes (JE and TIS10) in quiescent BALB/c 3T3 cells. Increases in cyclic AMP (cAMP) levels in response to CT are likely responsible for the induction of TIS10 gene expression, since treatment with 8-Br-cAMP and increasing the intracellular levels o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Qureshi SA,Alexandropoulos K,Joseph CK,Spangler R,Foster DA

    更新日期:1991-01-01 00:00:00

  • Mutant mouse models reveal the relative roles of E2F1 and E2F3 in vivo.

    abstract::The E2F1, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes. Here we use mutant mouse strains to investigate E2F3's role in vivo. We show that E2F3 is essential for embryonic viability in the pure 129...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cloud JE,Rogers C,Reza TL,Ziebold U,Stone JR,Picard MH,Caron AM,Bronson RT,Lees JA

    更新日期:2002-04-01 00:00:00

  • Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene.

    abstract::Human platelet-derived endothelial cell growth factor (hPD-ECGF) is a novel angiogenic factor which stimulates endothelial cell growth in vitro and promotes angiogenesis in vivo. We report here the cloning and sequencing of the gene for hPD-ECGF and its flanking regions. This gene is composed of 10 exons dispersed ove...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hagiwara K,Stenman G,Honda H,Sahlin P,Andersson A,Miyazono K,Heldin CH,Ishikawa F,Takaku F

    更新日期:1991-04-01 00:00:00

  • SDC25, a CDC25-like gene which contains a RAS-activating domain and is a dispensable gene of Saccharomyces cerevisiae.

    abstract::In the yeast Saccharomyces cerevisiae, the CDC25 gene product activates adenylate cyclase through RAS1 and RAS2 gene products. We have recently described the cloning of a DNA fragment which suppresses the cdc25 mutation but not ras1, ras2, or cdc35 mutations. This fragment contains a 5'-truncated open reading frame wh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Damak F,Boy-Marcotte E,Le-Roscouet D,Guilbaud R,Jacquet M

    更新日期:1991-01-01 00:00:00

  • cis-Acting determinants of heterochromatin formation on Drosophila melanogaster chromosome four.

    abstract::The heterochromatic domains of Drosophila melanogaster (pericentric heterochromatin, telomeres, and the fourth chromosome) are characterized by histone hypoacetylation, high levels of histone H3 methylated on lysine 9 (H3-mK9), and association with heterochromatin protein 1 (HP1). While the specific interaction of HP1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sun FL,Haynes K,Simpson CL,Lee SD,Collins L,Wuller J,Eissenberg JC,Elgin SC

    更新日期:2004-09-01 00:00:00

  • Novel functional residues in the core domain of histone H2B regulate yeast gene expression and silencing and affect the response to DNA damage.

    abstract::Previous studies have identified novel modifications in the core fold domain of histone H2B, but relatively little is known about the function of these putative histone modification sites. We have mutated core modifiable residues that are conserved in Saccharomyces cerevisiae histone H2B and characterized the effects ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kyriss MN,Jin Y,Gallegos IJ,Sanford JA,Wyrick JJ

    更新日期:2010-07-01 00:00:00

  • Diacylglycerol production in Xenopus laevis oocytes after microinjection of p21ras proteins is a consequence of activation of phosphatidylcholine metabolism.

    abstract::Microinjection of p21Ha-ras proteins into Xenopus laevis oocytes induces a rapid increase of 1,2-diacylglycerol (DAG) levels. The observed alterations in DAG levels were consistent with the ability of the protein to induce maturation, measured by germinal vesicle breakdown (GVBD). Both the increase in DAG levels and G...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lacal JC

    更新日期:1990-01-01 00:00:00

  • Phosphorylation of Jak2 on Ser(523) inhibits Jak2-dependent leptin receptor signaling.

    abstract::The leptin receptor, LRb, and other cytokine receptors are devoid of intrinsic enzymatic activity and rely upon the activity of constitutively associated Jak family tyrosine kinases to mediate intracellular signaling. In order to clarify mechanisms by which Jak2, the cognate LRb-associated Jak kinase, is regulated and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ishida-Takahashi R,Rosario F,Gong Y,Kopp K,Stancheva Z,Chen X,Feener EP,Myers MG Jr

    更新日期:2006-06-01 00:00:00

  • Wnt-1-inducing factor-1: a novel G/C box-binding transcription factor regulating the expression of Wnt-1 during neuroectodermal differentiation.

    abstract::The Wnt-1 proto-oncogene is essential for proper development of the midbrain and is expressed in a spatially and temporally restricted manner during central nervous system development in mice. In vitro, the gene is specifically transcribed during the retinoic acid (RA)-induced neuroectodermal differentiation of the P1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: St-Arnaud R,Moir JM

    更新日期:1993-03-01 00:00:00

  • Propranolol, atenolol, and trifluoperazine reduce the spontaneous occurrence of meiotic diploid products in Saccharomyces cerevisiae.

    abstract::The effect of atenolol, propranolol, trifluoperazine, and caffeine on the occurrence of meiotic diploid and disomic products in Saccharomyces cerevisiae was investigated. We demonstrated that atenolol, propranolol, and trifluoperazine reduce the occurrence of meiotic diploid products and that propranolol also slightly...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sora S,Bianchi M

    更新日期:1982-11-01 00:00:00

  • Identification of an upstream activating sequence and an upstream repressible sequence of the pyruvate kinase gene of the yeast Saccharomyces cerevisiae.

    abstract::To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UAS...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nishizawa M,Araki R,Teranishi Y

    更新日期:1989-02-01 00:00:00

  • Association of MEK1 with p21ras.GMPPNP is dependent on B-Raf.

    abstract::We have previously reported that immobilized p21ras forms a GMPPNP-dependent complex with a MEK activity. Furthermore, the association of the MEK activity was found to be independent of the presence of Raf-1. We have extended those observations to show that MEK1 is the MEK activity previously described to associate wi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Moodie SA,Paris MJ,Kolch W,Wolfman A

    更新日期:1994-11-01 00:00:00

  • NAD+-dependent deacetylase Hst1p controls biosynthesis and cellular NAD+ levels in Saccharomyces cerevisiae.

    abstract::Nicotine adenine dinucleotide (NAD(+)) performs key roles in electron transport reactions, as a substrate for poly(ADP-ribose) polymerase and NAD(+)-dependent protein deacetylases. In the latter two processes, NAD(+) is consumed and converted to ADP-ribose and nicotinamide. NAD(+) levels can be maintained by regenerat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bedalov A,Hirao M,Posakony J,Nelson M,Simon JA

    更新日期:2003-10-01 00:00:00

  • Nuclear factor I X deficiency causes brain malformation and severe skeletal defects.

    abstract::The transcription factor family of nuclear factor I (NFI) proteins is encoded by four closely related genes: Nfia, Nfib, Nfic, and Nfix. A potential role for NFI proteins in regulating developmental processes has been implicated by their specific expression pattern during embryonic development and by analysis of NFI-d...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Driller K,Pagenstecher A,Uhl M,Omran H,Berlis A,Gründer A,Sippel AE

    更新日期:2007-05-01 00:00:00

  • Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.

    abstract::Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Douglas P,Ye R,Morrice N,Britton S,Trinkle-Mulcahy L,Lees-Miller SP

    更新日期:2015-08-01 00:00:00

  • 2-Aminopurine selectively inhibits splicing of tumor necrosis factor alpha mRNA.

    abstract::2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Jarrous N,Osman F,Kaempfer R

    更新日期:1996-06-01 00:00:00

  • Carcinogenic nickel silences gene expression by chromatin condensation and DNA methylation: a new model for epigenetic carcinogens.

    abstract::A transgenic gpt+ Chinese hamster cell line (G12) was found to be susceptible to carcinogenic nickel-induced inactivation of gpt expression without mutagenesis or deletion of the transgene. Many nickel-induced 6-thioguanine-resistant variants spontaneously reverted to actively express gpt, as indicated by both reversi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lee YW,Klein CB,Kargacin B,Salnikow K,Kitahara J,Dowjat K,Zhitkovich A,Christie NT,Costa M

    更新日期:1995-05-01 00:00:00

  • Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26.

    abstract::The heat shock transcription factors (Hsfs) activate the stress-inducible expression of heat shock proteins (Hsps) and other molecular chaperones in response to stress and, therefore, play an essential role in protein disaggregation and protein folding. In humans, missense mutation in the hsf4 gene causes cataract, an...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hu Y,Mivechi NF

    更新日期:2006-04-01 00:00:00

  • Elements and factors involved in tissue-specific and embryonic expression of the liver transcription factor LFB1 in Xenopus laevis.

    abstract::LFB1 (HNF1) is a tissue-specific transcription factor found in the livers, stomachs, intestines, and kidneys of vertebrates. By analyzing the promoter of the Xenopus LFB1 gene, we identified potential autoregulation by LFB1 and regulation by HNF4, a transcription factor with a tissue distribution similar to that of LF...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zapp D,Bartkowski S,Holewa B,Zoidl C,Klein-Hitpass L,Ryffel GU

    更新日期:1993-10-01 00:00:00