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Titolo:
CREB BINDING-PROTEIN IS A REQUIRED COACTIVATOR FOR SMAD-DEPENDENT, TRANSFORMING-GROWTH-FACTOR-BETA TRANSCRIPTIONAL RESPONSES IN ENDOTHELIAL-CELLS
Autore:
TOPPER JN; DICHIARA MR; BROWN JD; WILLIAMS AJ; FALB D; COLLINS T; GIMBRONE MA;
Indirizzi:
STANFORD UNIV,SCH MED,FALK CARDIOVASC RES CTR,CV273,300 PASTEUR DR STANFORD CA 94305 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,VASC RES DIV,DEPT PATHOL BOSTON MA 02115 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CARDIOVASC DIV,DEPT MED BOSTON MA 02115 MILLENNIUM PHARMACEUT INC CAMBRIDGE MA 02139
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 16, volume: 95, anno: 1998,
pagine: 9506 - 9511
SICI:
0027-8424(1998)95:16<9506:CBIARC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAD-RELATED PROTEIN; TGF-BETA; SIGNALING PATHWAYS; CBP; RECEPTORS; P300/CBP; ENCODES; DPC4;
Keywords:
VASCULAR ENDOTHELIUM; P300; TRANSCRIPTION FACTORS; SIGNAL TRANSDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
J.N. Topper et al., "CREB BINDING-PROTEIN IS A REQUIRED COACTIVATOR FOR SMAD-DEPENDENT, TRANSFORMING-GROWTH-FACTOR-BETA TRANSCRIPTIONAL RESPONSES IN ENDOTHELIAL-CELLS", Proceedings of the National Academy of Sciences of the United Statesof America, 95(16), 1998, pp. 9506-9511

Abstract

The transforming growth factor-beta (TGF-beta) superfamily of growth factors and cytokines has been implicated in a variety of physiological and developmental processes within the cardiovascular system. Smad proteins are a recently described family of intracellular signaling proteins that transduce signals in response to TGF-beta superfamily ligands, We demonstrate by both a mammalian two-hybrid and a biochemical approach that human Smad2 and Smad4, two essential Smad proteins involved in mediating TGF-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator CREB binding protein (CBP). This interaction is specific in that it requires ligand (TGF-beta) activation and is mediated by the transcriptional activation domains of the Smad proteins. A closely related, but distinct endothelial-expressed Smad protein, Smad7, which does not activate transcription in endothelial tells, does not interact with CBP. Furthermore, Smad2,4-CBP interactions involve the GOON terminus of CBP, a region that interacts with other regulated transcription factors such as certain signal transduction and transcription proteinsand nuclear receptors, Smad-CBP interactions are required for Smad-dependent TGF-beta-induced transcriptional responses in endothelial cells, as evidenced by inhibition with overexpressed 12S E1A protein and reversal of this inhibition with exogenous CRP, This report demonstrates a functional interaction between Smad proteins and an essential component of the mammalian transcriptional apparatus (CBP) and extends ourinsight into how Smad proteins may regulate transcriptional responsesin many cell types. Thus, functional Smad-coactivator interactions may be an important locus of signal integration in endothelial cells.

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Documento generato il 28/09/20 alle ore 15:09:40