Cell apoptosis: Requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3
Cell apoptosis: Requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3
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DOI：
10.1016/j.molcel.2006.05.023
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发表时间：
2006-07-07
期刊：
影响因子：
16
通讯作者：
Dong, Zigang
中科院分区：
文献类型：
--
作者：
Lu, Chengrong;Zhu, Feng;Dong, Zigang
免疫荧光研究表明，H2 AX在电离辐射诱导的DNA双链断裂位点被磷酸化，并且是DNA损伤后将修复因子募集到核灶中所必需的。因此，H2 AX的功能被认为主要与DNA损伤的修复相关。在这里，我们报告了H2 AX在细胞凋亡中的功能。我们的数据表明，H2 AX被UVA激活的JNK磷酸化。我们还提供了证据表明，UVA诱导caspase-3和caspase激活的DNA酶（CAD）的活性在H2 AX野生型和H2 AX敲除小鼠胚胎成纤维细胞（MEF）。然而，DNA片段化仅发生在H2 AX野生型MEFs中。此外，H2 AX磷酸化是CAD体外引发的DNA降解的关键。综上所述，这些数据表明，H2 AX磷酸化是DNA梯形成所需的，但不是半胱天冬酶-3的激活所需的;并且JNK/H2 AX途径与半胱天冬酶-3/CAD途径合作，导致细胞凋亡。
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.