Zhang Xiaoyan, Wang Yanzhuang
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048.
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048
Mol Biol Cell. 2015 Jun 15;26(12):2242-51. doi: 10.1091/mbc.E15-01-0041. Epub 2015 Apr 22.
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.
在哺乳动物细胞中，高尔基体在细胞分裂的每个周期中遗传至子细胞是由一个拆卸和重新组装过程介导的，并且这个过程受到磷酸化和泛素化的精确控制。VCIP135（含缬酪肽蛋白p97/p47复合物相互作用蛋白，p135）是p97/p47介导的有丝分裂后高尔基体膜融合所需的一种去泛素化酶，在有丝分裂期间多个位点发生磷酸化。然而，磷酸化是否直接调节细胞周期中VCIP135的去泛素酶活性和高尔基体膜融合仍不清楚。我们发现，在有丝分裂早期，Cdk1在单个残基S130处对VCIP135的磷酸化足以使该酶失活并抑制p97/p47介导的高尔基体膜融合。在有丝分裂末期，VCIP135的S130去磷酸化，同时其去泛素酶活性恢复且高尔基体重新组装。我们的结果表明，磷酸化和泛素化通过VCIP135协同作用来控制细胞周期中的高尔基体膜动态变化。
