Src regulates the activity of SIRT2

You Hee Choi; Hangun Kim; Sung Ho Lee; Yun-Hye Jin; Kwang Youl Lee

doi:10.1016/j.bbrc.2014.06.117

Src regulates the activity of SIRT2

Biochem Biophys Res Commun. 2014 Jul 25;450(2):1120-5. doi: 10.1016/j.bbrc.2014.06.117. Epub 2014 Jul 1.

Authors

You Hee Choi¹, Hangun Kim², Sung Ho Lee¹, Yun-Hye Jin³, Kwang Youl Lee⁴

Affiliations

¹ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
² College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, South Korea.
³ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea. Electronic address: jinyune@hanmail.net.
⁴ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea. Electronic address: kwanglee@chonnam.ac.kr.

PMID: 24996174
DOI: 10.1016/j.bbrc.2014.06.117

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.

Keywords: Phosphorylation; Protein level; SIRT2; Src.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CSK Tyrosine-Protein Kinase
HEK293 Cells
Humans
MCF-7 Cells
Phosphorylation
Sirtuin 2 / metabolism*
src-Family Kinases / metabolism*

Substances

CSK Tyrosine-Protein Kinase
src-Family Kinases
CSK protein, human
SIRT2 protein, human
Sirtuin 2