title: APC/C(Cdh1)-dependent degradation of Cdc20 requires a phosphorylation on CRY-box by Polo-like kinase-1 during somatic cell cycle.
abstract: 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.
authors: Laboratory of Cell Cycle & Signal Transduction, World Class University, Department of NanoBioMedical Science, Dankook University, 29 Anseo-Dong, Cheonan-Si, Chungnam 330-714, South Korea.
authors: Sun-Yi
authors: SY
authors: Hyun
authors: Badmaarag
authors: B
authors: Sarantuya
authors: Hee-Jae
authors: HJ
authors: Lee
authors: Young-Joo
authors: YJ
authors: Jang
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology*; D016193:G1 Phase; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025801:Ubiquitin; D000097869:Polo-Like Kinase 1; C513384:CDH1 protein, human; C577488:CDC20 protein, human