The p18 Truncated Form of Bax Behaves Like a Bcl-2 Homology Domain 3-only Protein
| Autor: | François M. Vallette, Lisa Oliver, Pierre-François Cartron, Philippe Juin, Khaled Meflah |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Proteolysis
Apoptosis Mitochondrion Cleavage (embryo) Biochemistry Homology (biology) Bcl-2-associated X protein Cell Line Tumor Proto-Oncogene Proteins medicine Humans Molecular Biology DNA Primers bcl-2-Associated X Protein Base Sequence biology medicine.diagnostic_test Brain Neoplasms Calpain Glioma Cell Biology Molecular biology Mitochondria Proto-Oncogene Proteins c-bcl-2 biology.protein Alpha helix |
| Zdroj: | Journal of Biological Chemistry. 279:11503-11512 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m311922200 |
| Popis: | p21(Bax) is a pro-apoptotic member of the Bcl-2 family and is converted by calpain into a truncated form called p18(Bax). This proteolysis enhanced the apoptogenic properties of Bax by a mechanism not yet elucidated. We have shown recently that the first alpha helix (Halpha1) of p21(Bax) contained a mitochondrial addressing sequence, which appeared to be necessary for p21(Bax)-induced apoptosis (Cartron, P. F., Priault, M., Oliver, L., Meflah, K., Manon, S., and Vallette, F. M. (2003) J. Biol. Chem. 278, 11633-11641). This feature is in contradiction with the high apoptogenic profile of p18(Bax), because the Halpha1 is lost during the calpain cleavage of p21(Bax). We investigated the role of p18(Bax) in apoptosis and found that its activity required the presence of p21(Bax). In addition, p18(Bax) exhibited a higher affinity for Bcl-Xl than p21(Bax) did, a property that seems to be essential for the fulfillment of its pro-apoptotic role. In conclusion, calpain proteolysis converts the multi-domain p21(Bax) into a Bcl-2 homology 3-like protein capable of overcoming the inhibition of apoptosis due to Bcl-Xl. |
| Databáze: | OpenAIRE |
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