CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest
CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest
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CCDC134 与 hADA2a 相互作用，并在乙酰转移酶活性、DNA 损伤诱导的细胞凋亡和细胞周期停滞中充当 hADA2a 的调节剂
DOI：
10.1007/s00418-012-0932-5
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发表时间：
2012-07-01
影响因子：
2.3
通讯作者：
Qiu, Xiaoyan
中科院分区：
文献类型：
--
作者：
Huang, Jing;Zhang, Li;Qiu, Xiaoyan
人类转录衔接子hADA 2a是一个重要的组成部分，一般控制非去阻遏5（GCN 5）组蛋白乙酰转移酶复合物。在这里，我们报告，卷曲螺旋结构域包含134（CCDC 134），一种新的核蛋白，结合到hADA 2a，并提高了在非应激条件下的hADA 2a蛋白的稳定性。此外，发现CCDC 134通过hADA 2a参与p300/CBP相关因子（PCAF）复合物并影响复合物的组蛋白乙酰转移酶活性。我们还发现，CCDC 134增加了PCAF依赖的K320乙酰化的p53和p53蛋白的稳定性在hADA 2a过表达的存在。此外，我们证明了CCDC 134和hADA 2a之间相互作用的生物学意义。CCDC 134在紫外线照射后出现明显的核内聚集，内源性CCDC 134的敲低抑制了hADA 2a诱导的细胞凋亡活性和G1/S期细胞阻滞。总之，我们的研究结果表明，CCDC 134可能作为一种新的调节hADA 2a，并通过hADA 2a在PCAF复合物中发挥作用，影响其乙酰转移酶活性和UV诱导的DNA损伤修复。
Human transcriptional adaptor hADA2a is an important component of the general control nonderepressible 5 (GCN5) histone acetyltransferase complex. Here, we report that coiled-coil domain containing 134 (CCDC134), a novel nuclear protein, binds to hADA2a and enhances the stability of the hADA2a protein in unstressed conditions. Furthermore, CCDC134 was found to participate in the p300/CBP-associated factor (PCAF) complex via hADA2a and affect the histone acetyltransferase activity of the complex. We also found that CCDC134 increased the PCAF-dependent K320 acetylation of p53 and p53 protein stability in the presence of hADA2a overexpression. Moreover, we demonstrated the biological significance of the interaction between CCDC134 and hADA2a. CCDC134 showed obvious nuclear accumulation after ultraviolet (UV) irradiation, and the knockdown of endogenous CCDC134 suppressed hADA2a-induced cell apoptosis activity and G1/S cell cycle arrest. Together, our findings indicate that CCDC134 might act as a novel regulator of hADA2a, and plays roles in the PCAF complex via hADA2a to affect its acetyltransferase activity and UV-induced DNA damage repair.