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

Academic Article


  • 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 G2/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 G2/M phase progression. © 2013 Landes Bioscience.
  • Published In

  • Cell Cycle  Journal
  • Digital Object Identifier (doi)

    Author List

  • Xu Y; Yang H; Joo HY; Yu JH; Smith AD; Schneider D; Chow LT; Renfrow M; Wang H
  • Start Page

  • 3408
  • End Page

  • 3416
  • Volume

  • 12
  • Issue

  • 19