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 Citations (Scopus)

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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E2F1 Transcription Factor
Transforming Growth Factors
Growth
Cyclin-Dependent Kinases
E2F Transcription Factors
Tumor Suppressor Proteins
Mink
Human Adenoviruses
Retinoblastoma Protein
Oncogene Proteins
Epithelial Cells
Maintenance
RNA
Lung
Peptides
DNA

ASJC Scopus subject areas

  • General

Cite this

Expression of the E2F1 transcription factor overcomes type β transforming growth factor-mediated growth suppression. / Schwarz, James K; Bassing, Craig H.; Kovesdi, Imre; Datto, Michael B.; Blazing, Michael; George, Samuel; Wang, Xiao Fan; Nevins, Joseph R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 2, 17.01.1995, p. 483-487.

Research output: Contribution to journalArticle

Schwarz, James K ; Bassing, Craig H. ; Kovesdi, Imre ; Datto, Michael B. ; Blazing, Michael ; George, Samuel ; Wang, Xiao Fan ; Nevins, Joseph R. / Expression of the E2F1 transcription factor overcomes type β transforming growth factor-mediated growth suppression. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 2. pp. 483-487.
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