E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product.
Previous studies have shown that the carboxyl-terminal region of E2F-1 (residues 368-437) can support transcriptional activation when linked to the DNA- binding domain of the yeast transcription factor GAL4. This region also contains an 18-residue retinoblastoma (RB)-binding sequence, raising the possibility that RB binding might inhibit the ability of E2F-1 to form protein-protein contacts required for activation. Here we report a further analysis of the E2F-1 activation domain. In addition, we show that overexpression of RB, but not the RB mutant, RBd22, can inhibit GAL4/E2F-1 activity in vivo. Moreover, expression of the simian virus 40 large tumor antigen (T antigen), but not the RB- binding defective T antigen point mutant, K1, can overcome this repression. Three different GAL4/E2F-1 mutants that activate transcription, but fail to bind to RB, are not significantly affected by overexpression of RB. These findings support a model wherein RB suppresses E2F-1-mediated transcriptional activation through direct physical association.[1]References
- E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. Flemington, E.K., Speck, S.H., Kaelin, W.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
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