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

作者：Hyun Sun Yi; Sarantuya Badmaarag; Lee Hee Jae; Jang Young Joo^*

来源：Biochemical and Biophysical Research Communications, 2013, 436(1): 12-18.

DOI：10.1016/j.bbrc.2013.04.073

• Cdc20
• Degron
• CRY box
• APC/C-Cdh1
• Plk1
• Phosphorylation

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.

• 出版日期2013-6-21