SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation

	SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation
	Lau, AW; Liu, PD; Inuzuka, H; Gao, DM
刊名	AMERICAN JOURNAL OF CANCER RESEARCH
	2014
卷号	4 期号:3 页码:245-255
关键词	AMPK SIRT1 deacetylase DBC1 p53 phosphorylation acetylation
通讯作者	Gao, DM (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,hinuzuka@bidmc.harvard.edu ; dgao@sibcb.ac.cn
英文摘要	The deacetylase SIRT1 regulates multiple biological processes including cellular metabolism and aging. Importantly, SIRT1 can also inactivate the p53 tumor suppressor via deacetylation, suggesting a role in oncogenesis. Recently, SIRT1 was shown to be released from its endogenous inhibitor DBC1 by a process requiring AMPK and the phosphorylation of SIRT1 by yet undefined kinase(s). Here we provide further evidence that AMPK directly phosphorylates SIRT1 on T344, releasing it from DBC1. Furthermore, a phospho-mimetic SIRT1 (T334E) showed decreased binding to DBC1, supporting the importance of this phosphorylation in AMPK-mediated regulation of SIRT1 activity. In addition, inhibition of AMPK by Compound C led to increased p53 acetylation, suggesting a role for the AMPK/SIRT1 pathway in regulating p53 signaling. Together, our results support a hypothesis that AMPK negatively regulates p53 acetylation via phosphorylation of SIRT1 on T344. Furthermore, our findings also define the AMPK/SIRT1 axis as a possible targetable pathway to regulate p53 function.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	CELL-SURVIVAL ; DNA-DAMAGE ; DEPENDENT REGULATION ; CANCER CELLS ; DEACETYLASE ; PROMOTES ; DBC1 ; SKP2 ; TRANSCRIPTION ; DEGRADATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000341265600005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/168]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Lau, AW,Liu, PD,Inuzuka, H,et al. SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2014,4(3):245-255.
APA	Lau, AW,Liu, PD,Inuzuka, H,&Gao, DM.(2014).SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation.AMERICAN JOURNAL OF CANCER RESEARCH,4(3),245-255.
MLA	Lau, AW,et al."SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation".AMERICAN JOURNAL OF CANCER RESEARCH 4.3(2014):245-255.