title: VCIP135 acts as a deubiquitinating enzyme during p97-p47-mediated reassembly of mitotic Golgi fragments.
abstract: The AAA-ATPase p97/Cdc48 functions in different cellular pathways using distinct sets of adapters and other cofactors. Together with its adaptor Ufd1-Npl4, it extracts ubiquitylated substrates from the membrane for subsequent delivery to the proteasome during ER-associated degradation. Together with its adaptor p47, on the other hand, it regulates several membrane fusion events, including reassembly of Golgi cisternae after mitosis. The finding of a ubiquitin-binding domain in p47 raises the question as to whether the ubiquitin-proteasome system is also involved in membrane fusion events. Here, we show that p97-p47-mediated reassembly of Golgi cisternae requires ubiquitin, but is not dependent on proteasome-mediated proteolysis. Instead, it requires the deubiquitinating activity of one of its cofactors, VCIP135, which reverses a ubiquitylation event that occurs during mitotic disassembly. Together, these data reveal a cycle of ubiquitylation and deubiquitination that regulates Golgi membrane dynamics during mitosis. Furthermore, they represent the first evidence for a proteasome-independent function of p97/Cdc48.
authors.affiliation: Institute of Biochemistry, ETH Hoenggerberg, HPM G17.1, 8093 Zurich, Switzerland.
authors.forename: Yanzhuang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ayano
authors.initials: A
authors.lastname: Satoh
authors.forename: Graham
authors.initials: G
authors.lastname: Warren
authors.forename: Hemmo H
authors.initials: HH
authors.lastname: Meyer
authors.forename: Yangzhuang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D010450:Endopeptidases; D006056:Golgi Apparatus / Q000648:ultrastructure*; D008099:Liver / Q000502:physiology; D008561:Membrane Fusion; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D025801:Ubiquitin; D010450:Endopeptidases; C470473:Vcpip1 protein, rat; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C404942:p97 ATPase