title: Src regulates the activity of SIRT2.
abstract: SIRT2 is a mammalian member of the Sirtuin family of NAD(+)-dependent protein deacetylases. The tyrosine kinase Src is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. The function of SIRT2 is modulated by post-translational modifications; however, the precise molecular signaling mechanism of SIRT2 through interactions with c-Src has not yet been established. In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104. c-Src also showed the ability to regulate the deacetylation activity of SIRT2. Investigation on the phosphorylation of SIRT2 suggested that this was the method of c-Src-mediated SIRT2 regulation.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, South Korea.
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea. Electronic address: jinyune@hanmail.net.
authors.forename: Yun-Hye
authors.initials: YH
authors.lastname: Jin
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea. Electronic address: kwanglee@chonnam.ac.kr.
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D056565:Sirtuin 2 / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C474199:SIRT2 protein, human; D056565:Sirtuin 2
keywords: Phosphorylation; Protein level; SIRT2; Src