title: Cell cycle regulation of VCIP135 deubiquitinase activity and function in p97/p47-mediated Golgi reassembly.
abstract: In mammalian cells, the inheritance of the Golgi apparatus into the daughter cells during each cycle of cell division is mediated by a disassembly and reassembly process, and this process is precisely controlled by phosphorylation and ubiquitination. VCIP135 (valosin-containing protein p97/p47 complex-interacting protein, p135), a deubiquitinating enzyme required for p97/p47-mediated postmitotic Golgi membrane fusion, is phosphorylated at multiple sites during mitosis. However, whether phosphorylation directly regulates VCIP135 deubiquitinase activity and Golgi membrane fusion in the cell cycle remains unknown. We show that, in early mitosis, phosphorylation of VCIP135 by Cdk1 at a single residue, S130, is sufficient to inactivate the enzyme and inhibit p97/p47-mediated Golgi membrane fusion. At the end of mitosis, VCIP135 S130 is dephosphorylated, which is accompanied by the recovery of its deubiquitinase activity and Golgi reassembly. Our results demonstrate that phosphorylation and ubiquitination are coordinated via VCIP135 to control Golgi membrane dynamics in the cell cycle.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048 yzwang@umich.edu.
authors.forename: Yanzhuang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D016415:Sequence Alignment; D054875:Ubiquitination; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D010450:Endopeptidases; C581414:VCPIP1 protein, human; D000251:Adenosine Triphosphatases; C404942:p97 ATPase; C000614178:VCP protein, human; D000074405:Valosin Containing Protein