Bcl-2-induced changes in E2F regulatory complexes reveal the potential for integrated cell cycle and cell death functions Journal Article
| Authors: | Lind, E. F.; Wayne, J.; Wang, Q. Z.; Staeva, T.; Stolzer, A.; Petrie, H. T. |
| Article Title: | Bcl-2-induced changes in E2F regulatory complexes reveal the potential for integrated cell cycle and cell death functions |
| 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. |
| Keywords: | controlled study; protein expression; human cell; dna-binding proteins; flow cytometry; proteins; cell cycle proteins; cell death; cell survival; cell cycle; protein bcl 2; gene expression; cell line; genetic transcription; transfection; phosphorylation; transcription factors; gene expression regulation; transcription regulation; transcription factor e2f; carrier proteins; phosphoproteins; retinoblastoma protein; proto-oncogene proteins c-bcl-2; dna determination; retinoblastoma-like protein p130; macromolecular substances; culture media, conditioned; transcription factor dp1; interleukin-3; e2f transcription factors; humans; human; priority journal; article |
| Journal Title: | Journal of Immunology |
| Volume: | 162 |
| Issue: | 9 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 1999-05-01 |
| Start Page: | 5374 |
| End Page: | 5379 |
| Language: | English |
| PUBMED: | 10228014 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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