Cyclin dependent kinase 1–dependent activation of APC/C ubiquitin ligase
作者： K. Fujimitsu , M. Grimaldi , H. Yamano
关键词: Ubiquitin ligase 、 Ubiquitin 、 Phosphorylation 、 Cyclin-dependent kinase 1 、 Cyclin-dependent kinase 、 Chemistry 、 Bioinformatics 、 Kinase 、 APC/C activator protein CDH1 、 CDC20 、 Cell biology
摘要: Error-free genome duplication and segregation are ensured through the timely activation of ubiquitylation enzymes. The anaphase-promoting complex or cyclosome (APC/C), a multisubunit E3 ubiquitin ligase, is regulated by phosphorylation. However, mechanism remains elusive. Using systematic reconstitution analysis vertebrate APC/Cs under physiological conditions, we show how cyclin-dependent kinase 1 (CDK1) activates APC/C coordinated phosphorylation between Apc3 Apc1. Phosphorylation loop domains CDK1 in with p9/Cks2 (a CDK regulatory subunit) controlled loading coactivator Cdc20 onto APC/C. A phosphomimetic mutation introduced into Apc1 allowed to increase activity interphase. These results define previously unrecognized subunit-subunit communication over distance functional consequences potential therapeutic target, our findings may facilitate development specific inhibitors.
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