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

Citation
Ef. Lind et al., Bcl-2-induced changes in E2F regulatory complexes reveal the potential forintegrated cell cycle and cell death functions, J IMMUNOL, 162(9), 1999, pp. 5374-5379
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
162
Issue
9
Year of publication
1999
Pages
5374 - 5379
Database
ISI
SICI code
0022-1767(19990501)162:9<5374:BCIERC>2.0.ZU;2-E
Abstract
Proliferation and cell death are tightly linked fates during cell and tissu e differentiation. In the past few gears, it has been shown that Bcl-2 exhi bits 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 t he 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 co nditions 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 i n E2F complex formation are paralleled by an apparent increase in pRb regul atory 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 lending to cell death. These analyses reveal a mechanism for cell cycle regulation by Bcl-3 that occurs at the level of E2 F transcriptional activity. Further, since specific E2F activities are clea rly linked to the induction of cell death, these findings may help to conso lidate the cell survival and cell cycle effects of Bcl-2 through a common t ranscriptional mechanism.