title: Dynamic regulation of Emi2 by Emi2-bound Cdk1/Plk1/CK1 and PP2A-B56 in meiotic arrest of Xenopus eggs.
abstract: In vertebrates, unfertilized eggs are arrested at metaphase of meiosis II by Mos and Emi2, an inhibitor of the APC/C ubiquitin ligase. In Xenopus, Cdk1 phosphorylates Emi2 and both destabilizes and inactivates it, whereas Mos recruits PP2A phosphatase to antagonize the Cdk1 phosphorylation. However, how Cdk1 phosphorylation inhibits Emi2 is largely unknown. Here we show that multiple N-terminal Cdk1 phosphorylation motifs bind cyclin B1-Cdk1 itself, Plk1, and CK1δ/ε to inhibit Emi2. Plk1, after rebinding to other sites by self-priming phosphorylation, partially destabilizes Emi2. Cdk1 and CK1δ/ε sequentially phosphorylate the C-terminal APC/C-docking site, thereby cooperatively inhibiting Emi2 from binding the APC/C. In the presence of Mos, however, PP2A-B56β/ε bind to Emi2 and keep dephosphorylating it, particularly at the APC/C-docking site. Thus, Emi2 stability and activity are dynamically regulated by Emi2-bound multiple kinases and PP2A phosphatase. Our data also suggest a general role for Cdk1 substrate phosphorylation motifs in M phase regulation.
authors.affiliation: Department of Biology, Graduate School of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Isoda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sako
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nishino
authors.forename: Nobushige
authors.initials: N
authors.lastname: Nakajo
authors.forename: Munemichi
authors.initials: M
authors.lastname: Ohe
authors.forename: Takanori
authors.initials: T
authors.lastname: Ezaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kanemori
authors.forename: Daigo
authors.initials: D
authors.lastname: Inoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ueno
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sagata
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000378:metabolism*; D047389:Casein Kinase I / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division; D044783:F-Box Proteins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008540:Meiosis; D010063:Ovum / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D017231:Proto-Oncogene Proteins c-mos / Q000737:chemistry / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis; D000097869:Polo-Like Kinase 1
chemical_list: D016203:CDC2 Protein Kinase; D047389:Casein Kinase I; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D017231:Proto-Oncogene Proteins c-mos; D029867:Xenopus Proteins; D000097869:Polo-Like Kinase 1; C498166:FBXO43 protein, Xenopus; C515682:B56delta phosphatase, Xenopus