CCDC84 Acetylation Oscillation Regulates Centrosome Duplication by Modulating HsSAS-6 Degradation

摘要

In animal cells, centriole number is strictly controlledin order to guarantee faithful cell division and geneticstability, but the mechanism by which the accuracyof centrosome duplication is maintained is not fullyunderstood. Here, we show that CCDC84 constrainscentriole number by modulating APC/CCdh1-mediatedHsSAS-6 degradation. More importantly,CCDC84 acetylation oscillates throughout the cellcycle, and the acetylation state of CCDC84 at lysine31 is regulated by the deacetylase SIRT1 and theacetyltransferase NAT10. Deacetylated CCDC84 isresponsible for its centrosome targeting, and acetylatedCCDC84 promotes HsSAS-6 ubiquitination byenhancing the binding affinity of HsSAS-6 for Cdh1.Our findings shed new light on the function of (de)acetylation in centriole number regulation as well asrefine the established centrosome duplicationmodel.