Bcl-2-induced changes in E2F regulatory complexes reveal the potential for integrated cell cycle and cell death functions

Evan Lind, Jay Wayne, Qi Zhi Wang, Teodora Staeva, Amy Stolzer, Howard T. Petrie

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Abstract

Proliferation and cell death are tightly linked fates during cell and tissue differentiation. In the past few years, it has been shown that Bcl-2 exhibits a potent cell cycle inhibitory effect, in addition to its better known role in the antagonism of cell death. In the present study, we show that the cell cycle effects of Bcl-2 apparently occur at the level of E2F control of gene transcription. Under conditions of normal cell growth, or under conditions that lead to cell death in the absence of Bcl-2, bcl-2 expression results in a reduction of free (active) E2F isoforms and in an increase in the formation of higher-order (inactive) complexes. Bcl-2- induced changes in E2F complex formation are paralleled by an apparent increase in pRb regulatory activity, by the up-regulation of p130 protein expression, and by the formation of E2F/p130 complexes at the expense of those consisting of E2F/p107. Cells lacking bcl-2 expression respond to growth factor withdrawal in the opposite manner, by the liberation of E2F from inactivating complexes and by continued cell cycle leading to cell death. These analyses reveal a mechanism for cell cycle regulation by Bcl-2 that occurs at the level of E2F transcriptional activity. Further, since specific E2F activities are clearly linked to the induction of cell death, these findings may help to consolidate the cell survival and cell cycle effects of Bcl-2 through a common transcriptional mechanism.

Original languageEnglish (US)
Pages (from-to)5374-5379
Number of pages6
JournalJournal of Immunology
Volume162
Issue number9
Publication statusPublished - May 1 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Lind, E., Wayne, J., Wang, Q. Z., Staeva, T., Stolzer, A., & Petrie, H. T. (1999). Bcl-2-induced changes in E2F regulatory complexes reveal the potential for integrated cell cycle and cell death functions. Journal of Immunology, 162(9), 5374-5379.