Cell apoptosis: Requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3

被引:301
作者
Lu, Chengrong [1 ]
Zhu, Feng [1 ]
Cho, Yong-Yeon [1 ]
Tang, Faqing [1 ]
Zykova, Tatyana [1 ]
Ma, Wei-ya [1 ]
Bode, Ann M. [1 ]
Dong, Zigang [1 ]
机构
[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
关键词
D O I
10.1016/j.molcel.2006.05.023
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
Immunofluorescence studies have revealed that H2AX is phosphorylated at the sites of DNA double-strand breaks induced by ionizing radiation and is required for recruitment of repair factors into nuclear foci after DNA damage. Therefore, the function of H2AX is believed to be associated primarily with repair of DNA damage. Here, we report a function of H2AX in cellular apoptosis. Our data showed that H2AX is phosphorylated by UVA-activated JNK. We also provided evidence showing that UVA induces caspase-3 and caspase-activated DNase (CAD) activity in both H2AX wild-type and H2AX knockout mouse embryonic fibroblasts (MEFs). However, DNA fragmentation occurred only in H2AX wild-type MEFs. Furthermore, H2AX phosphorylation was critical for DNA degradation triggered by CAD in vitro. Taken together, these data indicated that H2AX phosphorylation is required for DNA ladder formation, but not for the activation of caspase-3; and the JNK/H2AX pathway cooperates with the caspase-3/CAD pathway resulting in cellular apoptosis.
引用
收藏
页码:121 / 132
页数:12
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