Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax.
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.
Toyota
Hiroko
H
Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Yanase
Noriko
N
Yoshimoto
Takayuki
T
Moriyama
Masami
M
Sudo
Tetsuo
T
Mizuguchi
Junichiro
J
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
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