title: Serum withdrawal up-regulates human SIRT1 gene expression in a p53-dependent manner.
abstract: SIRT1, a nicotinamide adenine dinucleotide (NAD(+))-dependent histone/protein deacetylase, has been extensively studied recently for its critical role in the regulation of physiology, calorie restriction and aging. Studies on laboratory mice showed that expression of SIRT1 can be induced by starvation in a p53-dependent manner and requires the p53-binding sites present in the Sirt1 promoter. However, it remains to be determined whether these findings based on rodents apply to human beings. In this paper, we characterized a putative p53-binding element in the human SIRT1 promoter that might be required for the up-regulation of SIRT1 in response to nutritional stress. The p53-binding site in the promoter of human SIRT1 is more deviant from the consensus sequence than the corresponding sequence in the mouse Sirt1. There is a C to A change at the second half site in human SIRT1, thus disrupting the core-binding element CWWG in the canonical RRRCWWGYYY. To test whether such sequence change would affect its binding with p53 and the SIRT1 expression under stress, we studied various human cell lines with different p53 status and cells with ectopic expression of functionally distinct p53. We found that serum withdrawal also up-regulates human SIRT1 gene expression in a p53-dependent manner and that the p53-binding element in SIRT1 is required for the up-regulation. Thus, the mechanism responsible for the regulation of SIRT1 expression by p53 is conserved between mice and human beings.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Linshan
authors.initials: L
authors.lastname: Shang
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Guimin
authors.initials: G
authors.lastname: Gao
authors.forename: Bingxi
authors.initials: B
authors.lastname: Chen
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020218:Response Elements / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D016895:Culture Media, Serum-Free; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; D056564:Sirtuin 1