VCIP135 deubiquitinase and its binding protein, WAC, in p97ATPase-mediated membrane fusion

Go Totsukawa, Yayoi Kaneko, Keiji Uchiyama, Hiroyuki Toh, Kaori Tamura, Hisao Kondo

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Two distinct p97 membrane fusion pathways are required for Golgi biogenesis: the p97/p47 and p97/p37 pathways. VCIP135 is necessary for both pathways, while its deubiquitinating activity is required only for the p97/p47 pathway. We have now identified a novel VCIP135-binding protein, WAC. WAC localizes to the Golgi as well as the nucleus. In Golgi membranes, WAC is involved in a complex containing VCIP135 and p97. WAC directly binds to VCIP135 and increases its deubiquitinating activity. siRNA experiments revealed that WAC is required for Golgi biogenesis. In an in vitro Golgi reformation assay, WAC was necessary only for p97/p47-mediated Golgi reassembly, but not for p97/p37-mediated reassembly. WAC is hence thought to function in p97/p47-mediated Golgi membrane fusion by activating the deubiquitinating function of VCIP135. We also showed that the two p97 pathways function in ER membrane fusion as well. An in vitro ER reformation assay revealed that both pathways required VCIP135 but not its deubiquitinating activity for their ER membrane fusion. This was consistent with the finding that WAC is unnecessary for p97-mediated ER membrane fusion.

Original languageEnglish
Pages (from-to)3581-3593
Number of pages13
JournalEMBO Journal
Issue number17
Publication statusPublished - Aug 31 2011

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


Dive into the research topics of 'VCIP135 deubiquitinase and its binding protein, WAC, in p97ATPase-mediated membrane fusion'. Together they form a unique fingerprint.

Cite this