Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation Journal Article
| Authors: | Vairo, G.; Soos, T. J.; Upton, T. M.; Zalvide, J.; DeCaprio, J. A.; Ewen, M. E.; Koff, A.; Adams, J. M. |
| Article Title: | Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation |
| Abstract: | Independent of its antiapoptotic function, Bcl-2 can, through an undetermined mechanism, retard entry into the cell cycle. Cell cycle progression requires the phosphorylation by cyclin-dependent kinases (Cdks) of retinoblastoma protein (pRB) family members to free E2F transcription factors. We have explored whether retarded cycle entry is mediated by the Cdk inhibitor p27 or the pRB family. In quiescent fibroblasts, enforced Bcl-2 expression elevated levels of both p27 and the pRB relative p130. Bcl-2 still slowed G1 progression in cells deficient in pRB but not in those lacking p27 or p130. Hence, pRB is not required, but both p27 and p130 are essential mediators. The ability of p130 to form repressive complexes with E2F4 is implicated, because the retardation by Bcl-2 was accentuated by coexpressed E2F4. A plausible relevant target of p130/E2F4 is the E2F1 gene, because Bcl- 2 expression delayed E2F1 accumulation during G1 progression and overexpression of E2F1 overrode the Bcl-2 inhibition. Hence, Bcl-2 appears to retard cell cycle entry by increasing p27 and p130 levels and maintaining repressive complexes of p130 with E2F4, perhaps to delay E2F1 expression. |
| Keywords: | controlled study; dna-binding proteins; nonhuman; proteins; animal cell; mouse; animals; cell cycle proteins; mice; gene; cell cycle; protein bcl 2; mice, inbred c57bl; mice, transgenic; transcription factors; nuclear proteins; transcription factor e2f; protein p27; carrier proteins; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; phosphoproteins; retinoblastoma protein; lymphocytes; proto-oncogene proteins c-bcl-2; protein p130; retinoblastoma-like protein p107; retinoblastoma-like protein p130; microtubule-associated proteins; transcription factor dp1; e2f1 transcription factor; e2f transcription factors; priority journal; article; e2f4 transcription factor |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 20 |
| Issue: | 13 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2000-07-01 |
| Start Page: | 4745 |
| End Page: | 4753 |
| Language: | English |
| DOI: | 10.1128/mcb.20.13.4745-4753.2000 |
| PUBMED: | 10848600 |
| PROVIDER: | scopus |
| PMCID: | PMC85901 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
