Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression

• Published in: Cell cycle (Georgetown, Tex.) Vol. 12; no. 19; pp. 3408 - 3416
• Main Authors: Xu, Yang, Yang, Huirong, Joo, Heui-Yun, Yu, Jei-Hwa, Smith IV, Archer, Schneider, David, Chow, Louise T., Renfrow, Matthew, Wang, Hengbin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.10.2013; Landes Bioscience
• Subjects: Amino Acid Motifs; CDC2 Protein Kinase - metabolism; CDK1; cell cycle; Cell Cycle Checkpoints; Cell Division; Cell Proliferation; CRM1; Exportin 1 Protein; G2 Phase; G2/M phase; gene expression; H2A deubiquitination; HeLa Cells; Humans; Karyopherins - metabolism; Phosphorylation; Receptors, Cytoplasmic and Nuclear - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Serine - metabolism; Ubiquitin Thiolesterase - chemistry; Ubiquitin Thiolesterase - genetics; Ubiquitin Thiolesterase - metabolism; Ubp-M; H2A deubiquitination; cell cycle; CDK1; CRM1; G2/M phase; phosphorylation; gene expression; Ubp-M
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.26278

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.