Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression.


Journal Article

Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G1 and is associated with decreased G1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, growth-suppressive state. A variety of recent experiments suggest that a functional target of Rb is the E2F transcription factor. In addition, the growth-suppressive effects of TGF-beta can be overcome by expression of viral oncogene products that dissociate E2F from Rb and Rb-related polypeptides. These results suggest the possibility that control of E2F may be a downstream event of TGF-beta action. Consistent with that possibility is the observation that E2F1 RNA levels are drastically reduced in TGF-beta-treated cells. We have also used a recombinant adenovirus containing the human E2F1 gene to overexpress the E2F1 product in mink lung epithelial cells that were growth arrested with TGF-beta. We find that overexpression of E2F1 can overcome the TGF-beta-mediated effect as measured by the activation of cellular DNA synthesis. These results suggest that a likely downstream target for the cyclin-dependent kinases, which are controlled by TGF-beta, is the activation of E2F.

Full Text

Duke Authors

Cited Authors

  • Schwarz, JK; Bassing, CH; Kovesdi, I; Datto, MB; Blazing, M; George, S; Wang, XF; Nevins, JR

Published Date

  • January 17, 1995

Published In

Volume / Issue

  • 92 / 2

Start / End Page

  • 483 - 487

PubMed ID

  • 7831315

Pubmed Central ID

  • 7831315

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.92.2.483


  • eng

Conference Location

  • United States