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.
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Acknowledgments
This work was supported by the National Natural Sciences Foundation of China (30901303), Research Fund for the Doctoral Program of Higher Education of China (20090001120033) and the National Science and Technology Major Projects of New Drugs (2012ZX09103301-032). We thank Prof. Dalong Ma (Peking University Center for Human Disease Genomics) for his comments and discussion, Pei Zhang (Peking University Third Hospital, Beijing, China) for her generous technical support.
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J. Huang and L. Zhang contributed equally to this work.
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418_2012_932_MOESM1_ESM.jpg
Supplemental figure 1 In vitro association between CCDC134 and hADA2a β-galactosidase activity of co-transformant yeast colonies grown on highly stringent media (SD/-LTH) , was assayed by a colony lift filter. (A) The positive yeast colonies after two-hybrid assay using CCDC134 bait plasmid to screen a human full-length cDNA library consisted of 1500 known genes associated with cell apoptosis, cell proliferation and cell cycle. (B) Negative sign (-) indicates co-transformation with pGB empty vector. Positive results of seven colonies grown on SD/-LTH were shown. 251x224mm (72 x 72 DPI) (JPEG 160 kb)
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Huang, J., Zhang, L., Liu, W. et al. CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest. Histochem Cell Biol 138, 41–55 (2012). https://doi.org/10.1007/s00418-012-0932-5
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DOI: https://doi.org/10.1007/s00418-012-0932-5