SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60.
The histone acetyltransferase TIP60, a frequent target of monoallelic loss in human carcinomas, can acetylate many substrates, including histones and p53, and thus promote apoptosis following UV radiation. Here we showed that TIP60 is autoacetylated in response to UV damage, which is critically important for TIP60 activation. Mechanistically we demonstrated that TIP60 autoacetylation leads to the dissociation of TIP60 oligomer and enhances its interaction with substrates. Moreover, we identified SIRT1 that specifically deacetylates TIP60 and negatively regulates TIP60 activity in vivo. Taken together, our data reveal TIP60 autoacetylation as a key step in the control of its histone acetyltransferase activity and function in response to DNA damage.
Wang
Jiadong
J
Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Chen
Junjie
J
D000107:Acetylation; D017209:Apoptosis; D045744:Cell Line, Tumor; D004249:DNA Damage; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008954:Models, Biological; D011485:Protein Binding; D034622:RNA Interference; D056564:Sirtuin 1 / Q000502:physiology*; D014466:Ultraviolet Rays
D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C447939:SIRT1 protein, human; D056564:Sirtuin 1