Bax conformational change is a crucial step for PUMA-mediated apoptosis in human leukemia

被引:70
作者
Liu, FT [1 ]
Newland, AC [1 ]
Jia, L [1 ]
机构
[1] Univ London, Barts & London Queen Marys Sch Med & Dent, Dept Haematol, London, England
关键词
apoptosis; Bax; BH3-only protein; Bcl-XL; PUMA;
D O I
10.1016/j.bbrc.2003.09.109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:956 / 962
页数:7
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