beta TrCP-mediated ubiquitylation regulates protein stability of Mis18 beta in a cell cycle-dependent manner

Abstract

Ubiquitin E3 ligases including SCF complex are key regulators of cell cycle. Here, we show that Mis18 beta, a component of Mis18 complex governing CENP-A localization, is a new substrate of beta TrCP-containing SCF complex. beta TrCP interacted with Mis18 beta exclusively during interphase but not during mitosis and mediated proteasomal degradation of Mis18 beta leading to the inactivation of Mis18 complex during interphase. In addition, uncontrolled stabilization of Mis18 beta caused cell death. Together, we propose that beta TrCP-mediated regulation of Mis18 beta stability is a mechanism to restrict centromere function of Mis18 beta complex from late mitosis to early G1 phase. (C) 2013 Elsevier Inc. All rights reserved.