title: Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression.
abstract: In eukaryotic cells, genomic DNA is organized into a chromatin structure, which not only serves as the template for DNA-based nuclear processes, but also as a platform integrating intracellular and extracellular signals. Although much effort has been spent to characterize chromatin modifying/remodeling activities, little is known about cell signaling pathways targeting these chromatin modulators. Here, we report that cyclin-dependent kinase 1 (CDK1) phosphorylates the histone H2A deubiquitinase Ubp-M at serine 552 (S552P), and, importantly, this phosphorylation is required for cell cycle progression. Mass spectrometry analysis confirmed Ubp-M is phosphorylated at serine 552, and in vitro and in vivo assays demonstrated that CDK1/cyclin B kinase is responsible for Ubp-M S552P. Interestingly, Ubp-M S552P is not required for Ubp-M tetramer formation, deubiquitination activity, substrate specificity, or regulation of gene expression. However, Ubp-M S552P is required for cell proliferation and cell cycle G 2/M phase progression. Ubp-M S552P reduces Ubp-M interaction with nuclear export protein CRM1 and facilitates Ubp-M nuclear localization. Therefore, these studies confirm that Ubp-M is phosphorylated at S552 and identify CDK1 as the enzyme responsible for the phosphorylation. Importantly, this study specifically links Ubp-M S552P to cell cycle G 2/M phase progression.
authors.affiliation: Department of Biochemistry and Molecular Genetics; University of Alabama at Birmingham; Birmingham, AL USA; State Key Laboratory of Cellular and Molecular Biology; College of Life Science; Hebei Normal University; Shijiazhuang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Huirong
authors.initials: H
authors.lastname: Yang
authors.forename: Heui-Yun
authors.initials: HY
authors.lastname: Joo
authors.forename: Jei-Hwa
authors.initials: JH
authors.lastname: Yu
authors.forename: Archer D
authors.initials: AD
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Schneider
authors.forename: Louise T
authors.initials: LT
authors.lastname: Chow
authors.forename: Matthew
authors.initials: M
authors.lastname: Renfrow
authors.forename: Hengbin
authors.initials: H
authors.lastname: Wang
mesh_terms: D020816:Amino Acid Motifs; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002455:Cell Division; D049109:Cell Proliferation; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012694:Serine / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D016203:CDC2 Protein Kinase; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D012694:Serine; D043222:Ubiquitin Thiolesterase; D000097606:Exportin 1 Protein; C118778:USP16 protein, human
keywords: CDK1; CRM1; G2/M phase; H2A deubiquitination; Ubp-M; cell cycle; gene expression; phosphorylation