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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.
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页码:956 / 962
页数:7
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