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- Title
The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry.
- Authors
Huang, David C. S.; O'Reilly, Lorraine A.; Strasser, Andreas; Cory, Suzanne
- Abstract
The Bcl-2 family of proteins regulate apoptosis, some antagonizing cell death and others facilitating it. It has recently been demonstrated that Bcl-2 not only inhibits apoptosis but also restrains cell cycle entry. We show here that these two functions can be genetically dissociated. Mutation of a tyrosine residue within the conserved N-terminal BH4 region had no effect on the ability of Bcl-2 or its closest homologs to enhance cell survival and did not prevent heterodimerization with death-enhancing family members Bax, Bak, Bad and Bik. Neither did this mutation override the growth-inhibitory effect of p53. However, on stimulation with cytokine or serum, starved quiescent cells expressing the mutant proteins re-entered the cell cycle much faster than those expressing comparable levels of wild-type proteins. When wild-type and Y28 mutant Bcl-2 were co-expressed, the mutant was dominant. Although R-Ras p23 has been reported to bind to Bcl-2, no interaction was detectable in transfected cells and R-Ras p23 did not interfere with the ability of Bcl-2 to inhibit apoptosis or cell cycle entry. These observations provide evidence that the anti-apoptotic function of Bcl-2 is mechanistically distinct from its inhibitory influence on cell cycle entry. Keywords: apoptosis; Bcl-2; Bcl-w; Bcl-xL; cell cycle control
- Subjects
APOPTOSIS; CELL cycle; TYROSINE; PROTEINS; GENETIC mutation; MOLECULAR biology
- Publication
EMBO Journal, 1997, Vol 16, Issue 15, p4628
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/16.15.4628