title: Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax.
abstract: Wild type (wt) p21 Bax was cleaved to generate p18 Bax during apoptotic processes by calpain, which was suggested to recognize a certain motif around amino acids 30-33 Phe-Ile-Gln-Asp (FIQD). In the present study, analysis of protein sequencing revealed that the cleavage site was between Gln28 and Gly29. The fragment lacking the NH(2)-terminal amino acids 1-28 (tBax(29)) was more apoptotic than wt Bax. The tBax(29)-induced apoptotic cell death was substantially resistant to Bcl-x(L)-mediated rescue, compared with wt Bax, in spite of the complex formation between these two molecules. Together, the tBax(29) would be valuable for the treatment of tumors with high levels of Bcl-x(L) as well as the understanding of Bax-mediated apoptotic processes.
authors.affiliation: Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Toyota
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanase
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Masami
authors.initials: M
authors.lastname: Moriyama
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sudo
authors.forename: Junichiro
authors.initials: J
authors.lastname: Mizuguchi
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D020816:Amino Acid Motifs; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000378:metabolism*; D002460:Cell Line / Q000187:drug effects; D003062:Codon; D003110:Colonic Neoplasms / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000196:embryology; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D003062:Codon; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D002154:Calpain