APC/C(Cdh1)-dependent degradation of Cdc20 requires a phosphorylation on CRY-box by Polo-like kinase-1 during somatic cell cycle.

Cdc20 is an activator of the anaphase-promoting complex (APC/C), and APC/C(Cdc20) is essential for metaphase-anaphase transition. To allow progression beyond mitosis, Cdc20 is degraded through KEN-box-dependent APC/C(Cdh1) activity. Mammalian Cdc20 contains the CRY box, a second APC/C(Cdh1)-dependent degron, but the molecular mechanism in degradation process remains undefined. Polo-like kinase-1 (Plk1) is an essential mitotic kinase regulating various targets in kinetochore, centrosome, and midbody for proper mitotic progression. Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase. The phosphorylation on serine-170 by Plk1 was important for ubiquitination and Cdh1-dependent proteolysis. However, this modification by Plk1 on CRY box had no effect on the subcellular localization of Cdc20 and the formation of APC/C-inhibitory checkpoint complexes under spindle assembly checkpoint. This mechanism will be the first finding of inhibitory phosphorylation related to Cdc20 instability.