title: The p18 truncated form of Bax behaves like a Bcl-2 homology domain 3-only protein.
abstract: 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.
authors.affiliation: Institut Fédératif de Recherche 26, INSERM U419, 44035 Nantes Cedex 01, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Cartron
authors.forename: Lisa
authors.initials: L
authors.lastname: Oliver
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
authors.forename: Khaled
authors.initials: K
authors.lastname: Meflah
authors.forename: François M
authors.initials: FM
authors.lastname: Vallette
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein