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

被引：71

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

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 310卷 / 03期

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

页码：956 / 962

页数：7

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