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

James K. Schwarz, Craig H. Bassing, Imre Kovesdi, Michael B. Datto, Michael Blazing, Samuel George, Xiao Fan Wang, Joseph R. Nevins

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Inhibition of cell growth by type β transforming growth factor (TGF-β) 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-β 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-β action. Consistent with that possibility is the observation that E2FI RNA levels are drastically reduced in TGF-β-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-β. We find that overexpression of E2F1 can overcome the TGF-β-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-β, is the activation of E2F.

Original languageEnglish (US)
Pages (from-to)483-487
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number2
DOIs
StatePublished - Jan 17 1995

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