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Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members.
- Source :
-
Cell death and differentiation [Cell Death Differ] 1999 Jun; Vol. 6 (6), pp. 525-32. - Publication Year :
- 1999
-
Abstract
- Certain Bcl-2 family members promote cell survival, whereas others promote apoptosis. To explore further how heterodimerization of opposing members affects survival activity, we have compared the abilities of the anti-apoptotic Bcl-w and A1 to bind to the pro-apoptotic Bax, Bak, Bad and Bik and to protect cells from their cytotoxic action. Bcl-w co-immunoprecipitated from cell lysates with Bax, Bak, Bad and Bik, but A1 bound only Bak and Bik. Mutation of A1 at a highly conserved glycine within the BH1 domain prevented binding, but the comparable Bcl-w mutant still bound Bak, Bad and Bik, indicating that the glycine is not essential for all heterodimerization. Bcl-w and A1 protected against apoptosis induced by over-expression of Bax or Bad but not that induced by Bak or Bik. With several gene pairs, binding and protection were discordant. The results may reflect critical threshold affinities but also suggest that certain pro-apoptotic proteins may also contribute to apoptosis by a mechanism independent of binding pro-survival proteins.
- Subjects :
- Animals
Apoptosis Regulatory Proteins
Binding Sites
Cell Line
Cell Survival
DNA-Binding Proteins genetics
Humans
Interleukin-3 metabolism
Interleukin-3 pharmacology
Mice
Minor Histocompatibility Antigens
Mitochondrial Proteins
Point Mutation
Proteins genetics
Replication Protein C
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
bcl-Associated Death Protein
Apoptosis
Carrier Proteins metabolism
DNA-Binding Proteins metabolism
Homeodomain Proteins
Membrane Proteins metabolism
Proteins metabolism
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Repressor Proteins
Saccharomyces cerevisiae Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 1350-9047
- Volume :
- 6
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell death and differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 10381646
- Full Text :
- https://doi.org/10.1038/sj.cdd.4400519