Nuclear function of Smad7 promotes myogenesis.

Abstract:

:In the "canonical" view of transforming growth factor beta (TGF-beta) signaling, Smad7 plays an inhibitory role. While Smad7 represses Smad3 activation by TGF-beta, it does not reverse the inhibitory effect of TGF-beta on myogenesis, suggesting a different function in myogenic cells. We previously reported a promyogenic role of Smad7 mediated by an interaction with MyoD. Based on this association, we hypothesized a possible nuclear function of Smad7 independent of its role at the level of the receptor. We therefore engineered a chimera of Smad7 with a nuclear localization signal (NLS), which serves to prevent and therefore bypass binding to the TGF-beta receptor while concomitantly constitutively localizing Smad7 to the nucleus. This Smad7-NLS did not repress Smad3 activation by TGF-beta but did retain its ability to enhance myogenic gene activation and phenotypic myogenesis, indicating that the nuclear, receptor-independent function of Smad7 is sufficient to promote myogenesis. Furthermore, Smad7 physically interacts with MyoD and antagonizes the repressive effects of active MEK on MyoD. Reporter and myogenic conversion assays indicate a pivotal regulation of MyoD transcriptional properties by the balance between Smad7 and active MEK. Thus, Smad7 has a nuclear coactivator function that is independent of TGF-beta signaling and necessary to promote myogenic differentiation.

journal_name

Mol Cell Biol

authors

Miyake T,Alli NS,McDermott JC

doi

10.1128/MCB.01005-09

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

722-35

issue

3

eissn

0270-7306

issn

1098-5549

pii

MCB.01005-09

journal_volume

30

pub_type

杂志文章
  • AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae.

    abstract::The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis. The function of AFR1 was investigated by engineering cells to constitutively express AFR1 without...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.2.723

    authors: Konopka JB,DeMattei C,Davis C

    更新日期:1995-02-01 00:00:00

  • Definition of the minimal simian virus 40 large T antigen- and adenovirus E1A-binding domain in the retinoblastoma gene product.

    abstract::It has previously been demonstrated that the simian virus 40 large T antigen and adenovirus E1A proteins can form complexes with the retinoblastoma susceptibility gene product (RB). We studied the ability of these proteins to bind to mutant RB proteins in vitro. A region of RB spanning residues 379 to 792 was found to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.7.3761

    authors: Kaelin WG Jr,Ewen ME,Livingston DM

    更新日期:1990-07-01 00:00:00

  • Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling.

    abstract::Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that carries out multiple functions. Although numerous observations suggest that PP2A plays a major role in downregulation of the mitogen-activated protein (MAP) kinase pathway, the precise mechanisms are unknown. To clarify the role of PP2A in...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.7.2375-2387.2002

    authors: Ugi S,Imamura T,Ricketts W,Olefsky JM

    更新日期:2002-04-01 00:00:00

  • B-myc inhibits neoplastic transformation and transcriptional activation by c-myc.

    abstract::B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also fun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.2.1130

    authors: Resar LM,Dolde C,Barrett JF,Dang CV

    更新日期:1993-02-01 00:00:00

  • The 3' untranslated region of tumor necrosis factor alpha mRNA is a target of the mRNA-stabilizing factor HuR.

    abstract::Posttranscriptional regulation is important for tumor necrosis factor alpha (TNF-alpha) expression in monocytes and macrophages, and an AU-rich element (ARE) in the 3' untranslated region (UTR) of TNF-alpha mRNA is implicated in control of its translation and mRNA stability. Regulation of mRNA turnover is thought to b...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.3.721-730.2001

    authors: Dean JL,Wait R,Mahtani KR,Sully G,Clark AR,Saklatvala J

    更新日期:2001-02-01 00:00:00

  • Deep intron elements mediate nested splicing events at consecutive AG dinucleotides to regulate alternative 3' splice site choice in vertebrate 4.1 genes.

    abstract::Distal intraexon (iE) regulatory elements in 4.1R pre-mRNA govern 3' splice site choice at exon 2 (E2) via nested splicing events, ultimately modulating expression of N-terminal isoforms of cytoskeletal 4.1R protein. Here we explored intrasplicing in other normal and disease gene contexts and found conservation of int...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05716-11

    authors: Parra MK,Gallagher TL,Amacher SL,Mohandas N,Conboy JG

    更新日期:2012-06-01 00:00:00

  • MAT1-modulated CAK activity regulates cell cycle G(1) exit.

    abstract::The cyclin-dependent kinase (CDK)-activating kinase (CAK) is involved in cell cycle control, transcription, and DNA repair (E. A. Nigg, Curr. Opin. Cell. Biol. 8:312-317, 1996). However, the mechanisms of how CAK is integrated into these signaling pathways remain unknown. We previously demonstrated that abrogation of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.1.260-270.2001

    authors: Wu L,Chen P,Shum CH,Chen C,Barsky LW,Weinberg KI,Jong A,Triche TJ

    更新日期:2001-01-01 00:00:00

  • Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity.

    abstract::In the mouse mammary tumor virus promoter, a tandem of octamer motifs, recognized by ubiquitous and tissue-restricted Oct transcription factors, is located upstream of the TATA box and next to a binding site for the transcription factor nuclear factor I (NF-I). Their function was investigated with mutant long terminal...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.2.1191

    authors: Buetti E

    更新日期:1994-02-01 00:00:00

  • Induction of yeast histone genes by stimulation of stationary-phase cells.

    abstract::In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.12.6356

    authors: Drebot MA,Veinot-Drebot LM,Singer RA,Johnston GC

    更新日期:1990-12-01 00:00:00

  • The Drosophila polycomb protein interacts with nucleosomal core particles In vitro via its repression domain.

    abstract::The proteins of the Polycomb group (PcG) are required for maintaining regulator genes, such as the homeotic selectors, stably and heritably repressed in appropriate developmental domains. It has been suggested that PcG proteins silence genes by creating higher-order chromatin structures at their chromosomal targets, t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.12.8451

    authors: Breiling A,Bonte E,Ferrari S,Becker PB,Paro R

    更新日期:1999-12-01 00:00:00

  • Adenine transport and binding in cultured mammalian cells deficient in adenine phosphoribosyltransferase.

    abstract::Rapid kinetic techniques were employed to measure the transport of adenine in adenine phosphoribosyltransferase-deficient L929 and Chinese hamster ovary (CHO) cells in zero-trans entry and exit and equilibrium exchange procedures. The kinetic parameters of transport were computed by fitting appropriate integrated rate...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.1.82

    authors: Puziss MB,Wohlhueter RM,Plagemann PG

    更新日期:1983-01-01 00:00:00

  • UbiA, the major polyubiquitin locus in Caenorhabditis elegans, has unusual structural features and is constitutively expressed.

    abstract::Ubiquitin is a multifunctional 76-amino-acid protein which plays critical roles in many aspects of cellular metabolism. In Caenorhabditis elegans, the major source of ubiquitin RNA is the polyubiquitin locus, UbiA. UbiA is transcribed as a polycistronic mRNA which contains 11 tandem repeats of ubiquitin sequence and p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.1.268

    authors: Graham RW,Jones D,Candido EP

    更新日期:1989-01-01 00:00:00

  • Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2.

    abstract::Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in integrin-mediated control of cell behavior. Following cell adhesion to components of the extracellular matrix, FAK becomes phosphorylated at multiple sites, including tyrosines 397, 576, and 577. Tyr-397 is an autophosphorylation site tha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.7.4806

    authors: Owen JD,Ruest PJ,Fry DW,Hanks SK

    更新日期:1999-07-01 00:00:00

  • Altered expression of heat shock proteins in embryonal carcinoma and mouse early embryonic cells.

    abstract::In a previous paper, we have shown that in the absence of stress, mouse embryonal carcinoma cells, like mouse early embryo multipotent cells, synthesize high levels of 89- and 70-kilodalton heat shock proteins (HSP)(O. Bensaude and M. Morange, EMBO J. 2:173-177, 1983). We report here the pattern of proteins synthesize...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.4.730

    authors: Morange M,Diu A,Bensaude O,Babinet C

    更新日期:1984-04-01 00:00:00

  • Role of histone N-terminal tails and their acetylation in nucleosome dynamics.

    abstract::Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4)(2) tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of hi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.19.7230-7237.2000

    authors: Morales V,Richard-Foy H

    更新日期:2000-10-01 00:00:00

  • RNA polymerase II accumulation in the promoter-proximal region of the dihydrofolate reductase and gamma-actin genes.

    abstract::The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) can be phosphorylated at serine 2 (Ser-2) and serine 5 (Ser-5) of the CTD heptad repeat YSPTSPS, and this phosphorylation is important in coupling transcription to RNA processing, including 5' capping, splicing, and polyadenylation. The mammalian endogen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.6.1961-1967.2003

    authors: Cheng C,Sharp PA

    更新日期:2003-03-01 00:00:00

  • Chromosomal double-strand breaks induce gene conversion at high frequency in mammalian cells.

    abstract::Double-strand breaks (DSBs) stimulate chromosomal and extrachromosomal recombination and gene targeting. Transcription also stimulates spontaneous recombination by an unknown mechanism. We used Saccharomyces cerevisiae I-SceI to stimulate recombination between neo direct repeats in Chinese hamster ovary (CHO) cell chr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6386

    authors: Taghian DG,Nickoloff JA

    更新日期:1997-11-01 00:00:00

  • Characterization of pp85, a target of oncogenes and growth factor receptors.

    abstract::An 85,000-molecular-weight polypeptide (85K polypeptide) has previously been identified as a common substrate for tyrosine phosphorylation upon polyomavirus middle T transformation or upon platelet-derived growth factor stimulation of 3T3 cells. In each case, pp85 has an associated phosphatidylinositol kinase activity...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2909

    authors: Cohen B,Liu YX,Druker B,Roberts TM,Schaffhausen BS

    更新日期:1990-06-01 00:00:00

  • The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells.

    abstract::The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (hPR-A and hPR-B). In most cell contexts, hPR-B functions as a transcriptional activator of progesterone-responsive genes, whereas hPR-A functions as a transcriptional inhibitor of all steroid hormone receptors...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.12.8356

    authors: Wen DX,Xu YF,Mais DE,Goldman ME,McDonnell DP

    更新日期:1994-12-01 00:00:00

  • The oncoprotein kinase chaperone CDC37 functions as an oncogene in mice and collaborates with both c-myc and cyclin D1 in transformation of multiple tissues.

    abstract::CDC37 encodes a 50-kDa protein that targets intrinsically unstable oncoprotein kinases including Cdk4, Raf-1, and v-src to the molecular chaperone Hsp90, an interaction that is thought to be important for the establishment of signaling pathways. CDC37 is required for proliferation in budding yeast and is coexpressed w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.12.4462-4473.2000

    authors: Stepanova L,Finegold M,DeMayo F,Schmidt EV,Harper JW

    更新日期:2000-06-01 00:00:00

  • Simian virus 40 large T-antigen point mutants that are defective in viral DNA replication but competent in oncogenic transformation.

    abstract::The large T antigen of simian virus 40 (SV40) is a multifunctional protein that is essential in both the virus lytic cycle and the oncogenic transformation of cells by SV40. To investigate the role of the numerous biochemical and physiological activities of T antigen in the lytic and transformation processes, we have ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.6.1125

    authors: Manos MM,Gluzman Y

    更新日期:1984-06-01 00:00:00

  • Tyrosyl and cyclic AMP-dependent protein kinase activities in BHK cells that express viral pp60src.

    abstract::Protein kinase activities were measured in Rous sarcoma virus-infected baby hamster kidney (BHK) cells that express v-src (BHK [v-src]) and compared with those of revertant and control BHK cells. We observed about a fivefold-higher tyrosine phosphorylating activity in BHK (v-src) cell extracts, which was due to src bu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.5.973

    authors: Clinton GM,Roskoski R Jr

    更新日期:1984-05-01 00:00:00

  • The KRAB zinc finger protein RSL1 regulates sex- and tissue-specific promoter methylation and dynamic hormone-responsive chromatin configuration.

    abstract::Over 400 Krüppel-associated box zinc finger proteins (KRAB-ZFPs) are encoded in mammalian genomes. While KRAB-ZFPs strongly repress transcription in vitro, little is known about their biological function or gene targets in vivo. Regulator of sex limitation 1 (Rsl1), one of the first KRAB-Zfp genes assigned a physiolog...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00615-12

    authors: Krebs CJ,Schultz DC,Robins DM

    更新日期:2012-09-01 00:00:00

  • MYC abrogates p53-mediated cell cycle arrest in N-(phosphonacetyl)-L-aspartate-treated cells, permitting CAD gene amplification.

    abstract::Genomic instability, including the ability to undergo gene amplification, is a hallmark of neoplastic cells. Similar to normal cells, "nonpermissive" REF52 cells do not develop resistance to N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of the synthesis of pyrimidine nucleotides, through amplification of cad, th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.1.536

    authors: Chernova OB,Chernov MV,Ishizaka Y,Agarwal ML,Stark GR

    更新日期:1998-01-01 00:00:00

  • Exon and intron sequences, respectively, repress and activate splicing of a fibroblast growth factor receptor 2 alternative exon.

    abstract::Two alternative exons, BEK and K-SAM, code for part of the ligand binding site of fibroblast growth factor receptor 2. Splicing of these exons is mutually exclusive, and the choice between them is made in a tissue-specific manner. We identify here pre-mRNA sequences involved in controlling splicing of the K-SAM exon. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.9.4825

    authors: Del Gatto F,Breathnach R

    更新日期:1995-09-01 00:00:00

  • DNA-binding activities of the Drosophila melanogaster even-skipped protein are mediated by its homeo domain and influenced by protein context.

    abstract::The homeo box gene even-skipped (eve) encodes a 376-amino-acid protein that binds with high affinity to sequences located near the 5' termini of the eve and en genes. The 5' en sites are A + T rich and contain copies of the 10-base-pair (bp) consensus sequence T-C-A-A-T-T-A-A-A-T. In contrast, the 5' eve sites are G +...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.11.4598

    authors: Hoey T,Warrior R,Manak J,Levine M

    更新日期:1988-11-01 00:00:00

  • Canonical Notch signaling is dispensable for early cell fate specifications in mammals.

    abstract::The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoder...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.21.9503-9508.2005

    authors: Shi S,Stahl M,Lu L,Stanley P

    更新日期:2005-11-01 00:00:00

  • Suppression of oxidative damage by Saccharomyces cerevisiae ATX2, which encodes a manganese-trafficking protein that localizes to Golgi-like vesicles.

    abstract::Oxygen toxicity in Saccharomyces cerevisiae lacking the copper/zinc superoxide dismutase (SOD1) can be suppressed by overexpression of the S. cerevisiae ATX2 gene. Multiple copies of ATX2 were found to reverse the aerobic auxotrophies of sod1(delta) mutants for lysine and methionine and also to enhance the resistance ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.11.6303

    authors: Lin SJ,Culotta VC

    更新日期:1996-11-01 00:00:00

  • A compartmentalized phosphorylation/dephosphorylation system that regulates U snRNA export from the nucleus.

    abstract::PHAX (phosphorylated adaptor for RNA export) is the key regulator of U snRNA nuclear export in metazoa. Our previous work revealed that PHAX is phosphorylated in the nucleus and is exported as a component of the U snRNA export complex to the cytoplasm, where it is dephosphorylated (M. Ohno, A. Segref, A. Bachi, M. Wil...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01189-07

    authors: Kitao S,Segref A,Kast J,Wilm M,Mattaj IW,Ohno M

    更新日期:2008-01-01 00:00:00

  • Transcription control region within the protein-coding portion of adenovirus E1A genes.

    abstract::A single-base deletion within the protein-coding region of the adenovirus type 5 early region 1A (E1A) genes, 399 bases downstream from the transcription start site, depresses transcription to 2% of the wild-type rate. Complementation studies demonstrated that this was due to two effects of the mutation: first, inacti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.7.1293

    authors: Osborne TF,Arvidson DN,Tyau ES,Dunsworth-Browne M,Berk AJ

    更新日期:1984-07-01 00:00:00