Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1.

ABSTRACT: Sirtuins (Sirt1-Sirt7) are NAD⁺-dependent protein deacetylases/ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16. Sirt7 restricts Sirt1 activity by preventing Sirt1 autodeacetylation causing enhanced Sirt1 activity in Sirt7^-/- mice. Increased Sirt1 activity in Sirt7^-/- mice blocks PPARγ and adipocyte differentiation, thereby diminishing accumulation o

SUBMITTER: Fang J 

PROVIDER: S-EPMC5635888 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature