Histone Deacetylase SIRT1 Targets Plk2 to Regulate Centriole Duplication

• Published in: Cell reports (Cambridge) Vol. 25; no. 10; pp. 2851 - 2865.e3
• Main Authors: Ling, Hongbo, Peng, Lirong, Wang, Jianbo, Rahhal, Raneen, Seto, Edward
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.12.2018; Elsevier
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.11.025

The protein deacetylase SIRT1 (Sirtuin 1) regulates many cellular processes, including cell-cycle progression, DNA damage response, and metabolism. Although the centrosome is a key regulator of cell-cycle progression and genome stability, little is known concerning SIRT1 controlled centrosome-associated events. Here we report that the centrosome protein Plk2 is acetylated and undergoes deacetylation by SIRT1. Acetylation protects Plk2 from ubiquitination, and SIRT1-mediated deacetylation promotes ubiquitin-dependent degradation of Plk2. SIRT1 controls centriole duplication by temporally modulating centrosomal Plk2 levels. AURKA phosphorylates SIRT1 and promotes the SIRT1-Plk2 interaction in mitosis. In early-mid G1, phosphorylated SIRT1 deacetylates and promotes Plk2 degradation. In late G1, SIRT1 is hypophosphorylated and its affinity to Plk2 is decreased, resulting in a rapid accumulation of centrosomal Plk2, which contributes to the timely initiation of centriole duplication. Collectively, our findings uncover a critical role of SIRT1 in centriole duplication and provide a mechanistic insight into SIRT1-mediated centrosome-associated functions. [Display omitted] •Plk2 is an acetylated centrosomal protein•SIRT1 deacetylates and destabilizes Plk2•SIRT1 controls the initiation of centriole duplication via targeting Plk2•AURKA phosphorylates SIRT1 and promotes SIRT1 deacetylation of Plk2 Ling et al. demonstrate that SIRT1 deacetylates and thereby destabilizes Plk2, which in turn results in the suppression of centriole duplication.