Ku70 is essential for histone deacetylase inhibitor trichostatin A-induced apoptosis.
Ku70 is essential for histone deacetylase inhibitor trichostatin A-induced apoptosis.
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Ku70 对于组蛋白脱乙酰酶抑制剂曲古抑菌素 A 诱导的细胞凋亡至关重要。
DOI：
10.3892/mmr.2015.3358
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发表时间：
2015-07
影响因子：
3.4
通讯作者：
Mei Qi-Bing
中科院分区：
文献类型：
--
作者：
Fan Lei;Sun Yang;Zhang He-Long;Mei Qi-Bing
先前有报道称，组蛋白去乙酰化酶抑制剂（HDACI） trichostatin A （TSA）可诱导结直肠癌（CRC）细胞中B细胞淋巴瘤2 （Bcl-2）相关X蛋白（Bax）依赖性凋亡。此外，Ku70已被确定为细胞凋亡的调节因子，其机制通过与Bax相互作用进行。本研究的目的是探讨Ku70在tsa诱导的CRC细胞系HCT116和HT29细胞凋亡中的作用。结果表明，TSA诱导Ku70乙酰化，并与细胞凋亡增加有关。此外，TSA处理促进Bax从其与Ku70的复合物中释放。然后检测到Bax从细胞质易位到线粒体，而细胞色素c从线粒体易位到细胞质。此外，使用小干扰RNA敲除Ku70可减少tsa诱导的细胞凋亡，并下调Bax的表达。通过蛋白酶体抑制剂MG132预处理细胞，这些效果得以恢复。综上所述，本研究结果提示Ku70乙酰化介导tsa诱导的CRC细胞凋亡。此外，由于Ku70在保护Bax免受蛋白体降解的作用，我们发现Ku70在tsa诱导的细胞凋亡中是不可或缺的。
It was previously reported that the histone deacetylase inhibitor (HDACI) trichostatin A (TSA) induced B cell lymphoma 2 (Bcl-2)-associated X protein (Bax)-dependent apoptosis in colorectal cancer (CRC) cells. In addition, Ku70 has been identified as a regulator of apoptosis, the mechanism of which proceeds via interacting with Bax. The aim of the present study was to investigate the role of Ku70 in TSA-induced apoptosis in the CRC cell lines HCT116 and HT29. The results showed that TSA induced the acetylation of Ku70, which was found to be associated with increased apoptosis. In addition, TSA treatment promoted the release of Bax from its complex with Ku70. Bax was then detected to have translocated from the cytoplasm into the mitochondria, while cytochrome c was detected to have translocated from the mitochondria into the cytoplasm. Furthermore, knockdown of Ku70 using small interfering RNA decreased TSA-induced apoptosis as well as downregulated the expression of Bax. These effects were rescued through pre-treatment of cells with the proteasome inhibitor MG132. In conclusion, the results of the present study suggested that Ku70 acetylation mediated TSA-induced apoptosis in CRC cells. In addition, Ku70 was found to be indispensable in TSA-induced apoptosis due to its role in protecting Bax from proteosomal degradation.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
4.3
作者：
R. Lindemann;B. Gabrielli;R. Johnstone
通讯作者：
R. Lindemann;B. Gabrielli;R. Johnstone
DOI：
10.1158/1541-7786.mcr-12-0065
发表时间：
2013-02
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Subramanian C;Hada M;Opipari AW Jr;Castle VP;Kwok RP
通讯作者：
Kwok RP
影响因子：
16
作者：
Cohen, HY;Lavu, S;Sinclair, DA
通讯作者：
Sinclair, DA
影响因子：
1.2
作者：
Koike, Manabu;Yutoku, Yasutomo;Koike, Aki
通讯作者：
Koike, Aki