A c-Fos- and E1A-interacting component of the tissue factor basal promoter complex mediates synergistic activation of transcription by transforming growth factor-beta1.

Published

Journal Article

Stimulation of quiescent mouse fibroblasts with TGF-beta1 and certain other growth factors result in cooperative activation of tissue factor (TF) gene transcription, an event accompanied by the rapid entry of c-Fos into specific AP-1 DNA-binding complexes (Felts et al. (1995) Biochemistry 34, 12355-12362). Here, we demonstrate that the ability of TGF-beta1 to synergistically activate TF transcription in serum-stimulated fibroblasts is dependent upon both c-Fos and a promoter-specific factor with functional properties characteristic of transcriptional coactivators. Inhibition of TF promoter activity by an adenovirus E1A mutant deleted in an essential CREB binding protein (CBP) interaction domain suggests that this factor is distinct from the CBP/p300 family of transcriptional coactivators. Importantly, the ability of this factor to mediate molecular interactions with c-Fos required for transcriptional synergism is directly linked to TGF-beta1 signaling. These data suggest a model in which a component of the TF basal transcription complex functions to integrate multiple signaling pathways required for full transcriptional activation of TF in fibroblasts.

Full Text

Duke Authors

Cited Authors

  • Felts, SJ; Stang, MT; Getz, MJ

Published Date

  • April 1997

Published In

Volume / Issue

  • 14 / 14

Start / End Page

  • 1679 - 1685

PubMed ID

  • 9135069

Pubmed Central ID

  • 9135069

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1201006

Language

  • eng