CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest.
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.
Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Haidian District 100191, Beijing, People's Republic of China.
Jing
J
Huang
Li
L
Zhang
Wei
W
Liu
Qinyuan
Q
Liao
Taiping
T
Shi
Lin
L
Xiao
Fanlei
F
Hu
Xiaoyan
X
Qiu
D000123:Acetyltransferases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C576232:CCDC134 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C097695:TADA2A protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000123:Acetyltransferases