Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response

被引：50

作者：

Cheng, Z. ^{[1
]}

Ke, Y. ^{[1
]}

Ding, X. ^{[2
,3
]}

Wang, F. ^{[1
,2
]}

Wang, H. ^{[1
]}

Ahmed, K. ^{[1
]}

Liu, Z. ^{[1
]}

Xu, Y. ^{[4
]}

Aikhionbare, F. ^{[2
]}

Yan, H. ^{[1
]}

Liu, J. ^{[1
]}

Xue, Y.

Powell, M. ^{[2
]}

Liang, S. ^{[5
]}

Reddy, S. E. ^{[2
]}

Hu, R. ^{[6
]}

Huang, H. ^{[4
]}

Jin, C. ^{[1
]}

Yao, X. ^{[1
,3
]}

机构：

[1] Hefei Natl Lab, Hefei, Peoples R China

[2] Morehouse Sch Med, Canc Biol Program, Atlanta, GA 30310 USA

[3] Beijing Univ Chinese Med, Dept Med, Beijing, Peoples R China

[4] Zhejiang Univ, Dept Hematol, Hangzhou, Peoples R China

[5] Hunan Normal Univ, Lab Protein chem, Changsha, Peoples R China

[6] Fudan Univ, Dept Endocrinol, Shanghai 200433, Peoples R China

来源：

ONCOGENE | 2008年 / 27卷 / 07期

关键词：

UV irradiation; DNA damage; TIP60; sumoylation; p53;

D O I：

10.1038/sj.onc.1210710

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The histone acetyltransferase TIP60 regulates the DNA damage response following genotoxic stress by acetylating histone and remodeling chromatin. However, the molecular mechanisms underlying the TIP60-dependent response to UV-induced DNA damage remain poorly understood. To systematically analyse proteins that regulate TIP60 activity in response to UVirradiation, we performed a proteomic analysis of proteins selectively bound to TIP60 in response to UVirradiation using mass spectrometry and identified a novel regulatory mechanism by which TIP60 orchestrates transcriptional activation of p53-dependent checkpoint response in UV-irradiated cells. The initial step of this pathway involves UV-induced association of TIP60 with SUMO-conjugation enzymes and site-specific sumoylation of TIP60 at lysines 430 and 451 via Ubc9. This sumoylation initiates the relocation of TIP60 from nucleoplasm to the promyelocytic leukemia body, which is essential for the UV-irradiated DNA damage repair response via a p53-dependent pathway. Significantly, inhibition of TIP60 sumoylation by overexpression of non-sumoylatable mutant abrogates the p53-dependent DNA damage response, demonstrating the importance of TIP60 sumoylation in response to UV irradiation. Our biochemical characterization demonstrated that the sumoylation of TIP60 augments its acetyltransferase activity in vitro and in vivo. Thus, this study shed new light on the function and regulation of TIP60 activity in UV-irradiated DNA damage response.

引用

页码：931 / 941

页数：11

共 22 条

[1] The diverse functions of histone acetyltransferase complexes [J].