title: Mitotic phosphorylation of MPP8 by cyclin-dependent kinases regulates chromatin dissociation.
abstract: Repressive epigenetic modifications, DNA methylation at CpG sites and histone H3 lysine 9 (H3K9) methylation, are enriched in heterochromatin, which undergoes drastic changes in structure during mitosis. MPP8 (M phase phosphoprotein 8) has been proposed to regulate positive association between these two repressive modifications, but actual involvement of this protein in changes in the heterochromatin structure during mitosis remains elusive. We demonstrate here that MPP8 predominantly localized to, but dissociated from, chromatin during interphase and early mitosis, respectively. Chromatin dissociation from MPP8 appeared to correlate with the phosphorylation status of MPP8. Experiments using inhibitors of various mitotic kinases demonstrated that the chromatin dissociation of MPP8 during metaphase to anaphase was specifically regulated by cyclin B1-Cdk1. Indeed, cyclin B1-Cdk1 effectively phosphorylated MPP8 in vitro and on STA mutant of MPP8 (all possible sites phosphorylated by Cdk were substituted by alanine) failed to dissociate from chromatin during early mitosis. Taken together, our results indicate that the chromatin association of MPP8 is regulated by Cdk-dependent phosphorylation.
authors: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Nagoya 467-8601, Japan.
authors: Makoto
authors: M
authors: Nishigaki
authors: Yu
authors: Y
authors: Kawada
authors: Toshinori
authors: T
authors: Misaki
authors: Kazuhiro
authors: K
authors: Murata
authors: Takahiro
authors: T
authors: Goshima
authors: Takahisa
authors: T
authors: Hirokawa
authors: Chisato
authors: C
authors: Yamada
authors: Midori
authors: M
authors: Shimada
authors: Makoto
authors: M
authors: Nakanishi
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D056744:Cyclin B1 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: C534699:CCNB1 protein, human; D002843:Chromatin; D056744:Cyclin B1; C547278:MPHOSPH8 protein, human; D010750:Phosphoproteins; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases