Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression - PubMed (original) (raw)
Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression
J K Schwarz et al. Proc Natl Acad Sci U S A. 1995.
Abstract
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.
References
- Mol Cell Biol. 1993 Mar;13(3):1610-8 - PubMed
- Nature. 1993 Dec 16;366(6456):704-7 - PubMed
- EMBO J. 1993 Mar;12(3):1013-20 - PubMed
- Science. 1993 Apr 23;260(5107):536-9 - PubMed
- Cell. 1993 May 7;73(3):487-97 - PubMed
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