Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea.
Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, South Korea.
Biochem Biophys Res Commun. 2014 Jan 3;443(1):62-7. doi: 10.1016/j.bbrc.2013.11.058. Epub 2013 Nov 21.
Ubiquitin E3 ligases including SCF complex are key regulators of cell cycle. Here, we show that Mis18β, a component of Mis18 complex governing CENP-A localization, is a new substrate of βTrCP-containing SCF complex. βTrCP interacted with Mis18β exclusively during interphase but not during mitosis and mediated proteasomal degradation of Mis18β leading to the inactivation of Mis18 complex during interphase. In addition, uncontrolled stabilization of Mis18β caused cell death. Together, we propose that βTrCP-mediated regulation of Mis18β stability is a mechanism to restrict centromere function of Mis18 complex from late mitosis to early G1 phase.
泛素 E3 连接酶包括 SCF 复合物是细胞周期的关键调节剂。在这里，我们表明，Mis18β，一个调控着 CENP-A 定位的 Mis18 复合物的组成部分，是含有βTrCP 的 SCF 复合物的一个新底物。βTrCP 在间期与 Mis18β 特异性相互作用，但在有丝分裂期间不相互作用，并介导 Mis18β 的蛋白酶体降解，导致间期 Mis18 复合物的失活。此外，Mis18β 的失控稳定导致细胞死亡。总之，我们提出βTrCP 介导的 Mis18β 稳定性的调节是一种机制，可限制 Mis18 复合物的着丝粒功能从有丝分裂后期到早期 G1 期。
