The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry
- Author(s)
- Huang, DCS; OReilly, LA; Strasser, A; Cory, S;
- Details
- Publication Year 1997-08-01,Volume 16,Issue #15,Page 4628-4638
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- 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 Bar, Bah, 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 wildtype 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.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- ADENOVIRUS E1B 19K; R-RAS; PROTEIN IDENTIFICATION; CONSERVED DOMAINS; TRANSGENIC MICE; HOMOLOG BAK; B-CELLS; C-MYC; PRE-B; DEATH
- Publisher's Version
- https://doi.org/10.1093/emboj/16.15.4628
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1997-08-01 12:00:00