Regulation of ku70-bax complex in cells.
Regulation of ku70-bax complex in cells.
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DOI：
10.4137/jcd.s13695
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kwok RP
中科院分区：
文献类型：
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作者：
Hada M;Kwok RP
Ku70是细胞核中的DNA修复因子，也通过与细胞质中的凋亡蛋白Bax结合来调节细胞死亡。Ku70的乙酰化触发Bax释放，导致Bax依赖性细胞死亡。因此，通过抑制使Ku70去乙酰化的组蛋白去乙酰化酶6 （HDAC6）或增加Ku70乙酰化，Bax与Ku70分离可诱导细胞死亡。我们的研究结果表明，在神经母细胞瘤细胞中，Ku70的缺失导致bax依赖性细胞死亡。该模型为筛选Ku70乙酰化调节剂提供了基本原理，这些调节剂可以单独或与放疗或dna损伤剂联合用于治疗癌症的临床试验中进行测试。
Ku70, a DNA repair factor in the nucleus, also regulates cell death by binding to the apoptotic protein Bax in the cytoplasm. Acetylation of Ku70 triggers Bax release resulting in Bax dependent cell death. Thus dissociating Bax from Ku70, either by inhibiting histone deacetylase 6 (HDAC6) that deacetylates Ku70 or by increasing Ku70 acetylation induces cell death. Our results showed that in neuroblastoma cells, the depletion of Ku70 results in Bax-dependent cell death. This model provides a rationale for screening Ku70 acetylation modulators that can be tested in clinical trials, either alone or in combination with radiotherapy or DNA-damaging agents for the treatment of cancer.