1. CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest.
- Author
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Huang J, Zhang L, Liu W, Liao Q, Shi T, Xiao L, Hu F, and Qiu X
- Subjects
- Acetyltransferases metabolism, Adaptor Proteins, Signal Transducing genetics, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cyclin-Dependent Kinase Inhibitor p21 genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA-Binding Proteins, HEK293 Cells, Humans, Membrane Proteins, Neoplasm Proteins genetics, Nuclear Proteins genetics, Transcription Factors genetics, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Adaptor Proteins, Signal Transducing metabolism, Apoptosis, Cell Cycle Checkpoints physiology, DNA Damage, Neoplasm Proteins metabolism, Nuclear Proteins metabolism, Transcription Factors metabolism
- Abstract
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.
- Published
- 2012
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