文章基本信息

标题：Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1
本地全文：下载
作者：Jian Fang ; Alessandro Ianni ; Christian Smolka 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：40
页码：E8352-E8361
DOI：10.1073/pnas.1706945114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 of white fat. Thus, reduction of Sirt1 activity restores adipogenesis in Sirt7^−/− adipocytes in vitro and in vivo. We disclosed a principle controlling Sirt1 activity and uncovered an unexpected complexity in the crosstalk between two different sirtuins. We propose that antagonistic interactions between Sirt1 and Sirt7 are pivotal in controlling the signaling network required for maintenance of adipose tissue.
关键词：sirtuin ; acetylation ; adipogenesis