VCIP135 acts as a deubiquitinating enzyme during p97–p47-mediated reassembly of mitotic Golgi fragments

Y Wang, A Satoh, G Warren, HH Meyer - The Journal of cell biology, 2004 - rupress.org
Y Wang, A Satoh, G Warren, HH Meyer
The Journal of cell biology, 2004rupress.org
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 …
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.
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