Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Haidian District 100191, Beijing, People's Republic of China.
Histochem Cell Biol. 2012 Jul;138(1):41-55. doi: 10.1007/s00418-012-0932-5. Epub 2012 May 30.
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.
人源转录接头蛋白 hADA2a 是一般控制非阻遏物 5（GCN5）组蛋白乙酰转移酶复合物的重要组成部分。在此，我们报告卷曲螺旋结构域包含蛋白 134（CCDC134），一种新型核蛋白，与 hADA2a 结合，并在未受应激的条件下增强 hADA2a 蛋白的稳定性。此外，CCDC134 被发现通过 hADA2a 参与 p300/CBP 相关因子（PCAF）复合物，并影响该复合物的组蛋白乙酰转移酶活性。我们还发现，在 hADA2a 过表达的情况下，CCDC134 增加了 PCAF 依赖性的 p53 K320 乙酰化和 p53 蛋白稳定性。此外，我们证明了 CCDC134 和 hADA2a 之间相互作用的生物学意义。CCDC134 在紫外线（UV）照射后表现出明显的核积累，而内源性 CCDC134 的敲低抑制了 hADA2a 诱导的细胞凋亡活性和 G1/S 细胞周期阻滞。总之，我们的研究结果表明，CCDC134 可能作为 hADA2a 的一种新型调节剂，通过 hADA2a 影响 PCAF 复合物的乙酰转移酶活性和 UV 诱导的 DNA 损伤修复。
