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Nat Commun. 2014 Aug 26;5:4735. doi: 10.1038/ncomms5735.

ArhGAP30 promotes p53 acetylation and function in colorectal cancer.

Author information

1
1] State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Rd, Shanghai 200001, China [2].
2
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Rd, Shanghai 200001, China.
3
School of Life Sciences, University of Science and Technology of China, Anhui 230027, China.
4
Research Center for Translational Medicine, East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
5
Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.

Abstract

Covalent modification adding acetyl groups to the C terminus of the p53 protein has been suggested to be required for its functional activation as a tumour suppressor. However, it remains largely unknown how p53 acetylation is deregulated in colorectal cancer (CRC), which is the third most commonly diagnosed cancer worldwide. Here we show that ArhGAP30, a Rho GTPase-activating protein, is a pivotal regulator for p53 acetylation and functional activation in CRC. ArhGAP30 binds to p53 C-terminal domain and P300, facilitating P300-mediated acetylation of p53 at lysine 382. ArhGAP30 expression is required for p53 activation upon DNA damage stress, and the level of ArhGAP30 correlates with p53 acetylation and functional activation in CRC tissues. Moreover, low level of ArhGAP30 expression associates with poor survival of CRC patients. In summary, ArhGAP30 is required for p53 acetylation and functional activation in CRC, and the expression of ArhGAP30 is a potential prognostic marker for CRC.

PMID:
25156493
DOI:
10.1038/ncomms5735
[Indexed for MEDLINE]

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