Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 310, Issue 3, Pages 956-962Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2003.09.109
Keywords
apoptosis; Bax; BH3-only protein; Bcl-XL; PUMA
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The BH3-only protein, PUMA, plays an important role in p53-mediated apoptosis. The apoptotic effect of PUMA on the mitochondria was studied using a p53-negative, human leukemia K562 cell line. Overexpression of PUMA was accompanied by an increased Bax expression, Bax conformational change, and translocation to mitochondria. A PUMA-BH3 peptide can induce Bax conformational change, cytochrome c release, and reduction in the mitochondrial membrane potential (Deltapsi(m)) in isolated K562 mitochondria and can be inhibited by Bcl-XL. The homo-dimer of Bax/Bax was also weakly shown after mitochondria were treated with PUMA-BH3 peptide but may not be lethal for PUMA-induced apoptosis in K562 cells. Our results suggest that PUMA-induced Bax conformational change and Bax translocation to mitochondria can be separate events and the conformational change in Bax is crucial for PUMA-induced mitochondrial dysfunction. (C) 2003 Elsevier Inc. All rights reserved.
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