Yiqi Qian

SIRT1 is an NAD+-dependent deacetylase that plays important roles in many biological functions.  Our lab determined that multi-functional sorting protein PACS-2 is an in vivo inhibitor of SIRT1. In response to DNA damage, PACS-2 promotes cell survival by inhibiting SIRT1-mediated p53 deacetylation to increase p21 expression and p21-dependent cell cycle arrest. In vitro assays and yeast two-hybrid assays show that PACS-2 binds to a disordered region of the SIRT1 N-terminal domain which is non-essential for enzyme activity. A clear map of PACS-2 SIRT1 interaction to identify the residues required for binding, combined with quantitative enzyme assays of kinetic studies will help us better understand the mechanism by which PACS-2 inhibits SIRT1 and the functions of this regulation in biological processes.