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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-01-0211. This Article Full Text (PDF) All Versions of this Article: 2003-01-0211v1 102/7/2605    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cao, X. Articles by May, W S. Search for Related Content PubMed PubMed Citation Articles by Cao, X. Articles by May, W S. Social Bookmarking                   What's this? Submitted January 23, 2003 Accepted June 5, 2003 Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis and a cathepsin-like protease may rapidly degrade p18 Bax Xuefang Cao, Xingming Deng, and W Stratford May* UF Shands Cancer Center and Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA * Corresponding author; email: smay{at}ufscc.ufl.edu. Bax is cleaved by calpain at aspartate 33 (D33) to yield p18 Bax during stress-induced apoptosis. To assess the role of p18 Bax in apoptosis, an ecdysone-inducible expression system was generated. Similar levels of WT and non-cleavable D33A (AspAla) Bax are induced in 293 cells while expression of N-terminal deleted p18 (1-33) Bax remains low (20% of full-length p21 Bax) due to a reduced half-life (2h vs. 12h for p21 Bax) resulting from increased sensitivity to cathepsin-like proteolytic degradation. P18 Bax expression is enhanced to levels comparable to p21 Bax when induction is carried out in the presence of cathepsin inhibitors, Z-Phe-Gly-NHO-Bz or N-Acetyl-Leu-Leu-Met-CHO. Compared with WT Bax, expression of similar levels of p18 Bax and surprisingly D33A Bax more potently induces apoptosis as indicated by increased cytochrome c release, caspase-9/-3 activation and DNA fragmentation, potentially due to their increased homo-oligomerization in mitochondrial membranes. Studies in A-549, U-937, K-562 and HL-60 cells confirm that inhibition of Bax cleavage results in 25-35% reduction of drug-induced apoptosis, while inhibition of p18 Bax degradation enhances apoptosis by 25-40%. Results indicate that although cleavage to p18 Bax is not required for Bax to initiate apoptosis, p18 Bax potently accelerates the apoptotic process. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. S. Mader, N. 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