Reaction: CDK1 phosphorylates VCPIP1
- in pathway: Ovarian tumor domain proteases
Valosin-containing protein p97/p47 complex-interacting protein 1 (VCPIP1, VCIP135) enzymatic activity is required for p97/p47 (VCP/NSFL1C) -mediated Golgi membrane fusion (Wang et al. 2004). In vitro it displays highest activity toward K11- and K48-linked ubiquitin chains (Mevissen et al. 2013, Zhang & Wang 2015).
VCPIP1 is highly phosphorylated in mitosis. This reduces its association with Golgi membranes and its interaction with VCP and is thought to regulate VCP function in the fusion of the postmitotic Golgi membrane (Zhang et al. 2014).
The N-terminal half of VCPIP1 has a single phosphorylation site, S131 (Zhang et al. 2014). A S131A mutant (serine mutated to alanine) exhibited strong DUB activity, while a phosphomimetic S131E (serine mutated to glutamic acid) mutant had no detectable activity suggesting that S131 phosphorylation regulates VCPIP1 DUB activity. Phosphorylation of VCPIP1 by CDK1 at S131 was sufficient to inactivate the enzyme and inhibit p97/p47-mediated Golgi membrane fusion. Dephosphorylation of VCPIP1 with the CDK1 inhibitor roscovitine significantly increased the DUB activity of endogenous VCPIP1 and attenuated p97/p47-mediated Golgi membrane fusion (Zhang & Wang 2015).
VCPIP1 is highly phosphorylated in mitosis. This reduces its association with Golgi membranes and its interaction with VCP and is thought to regulate VCP function in the fusion of the postmitotic Golgi membrane (Zhang et al. 2014).
The N-terminal half of VCPIP1 has a single phosphorylation site, S131 (Zhang et al. 2014). A S131A mutant (serine mutated to alanine) exhibited strong DUB activity, while a phosphomimetic S131E (serine mutated to glutamic acid) mutant had no detectable activity suggesting that S131 phosphorylation regulates VCPIP1 DUB activity. Phosphorylation of VCPIP1 by CDK1 at S131 was sufficient to inactivate the enzyme and inhibit p97/p47-mediated Golgi membrane fusion. Dephosphorylation of VCPIP1 with the CDK1 inhibitor roscovitine significantly increased the DUB activity of endogenous VCPIP1 and attenuated p97/p47-mediated Golgi membrane fusion (Zhang & Wang 2015).
Reaction - small molecule participants:
ADP [endoplasmic reticulum lumen]
ATP [endoplasmic reticulum lumen]
Reactome.org reaction link: R-HSA-8940100
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
ADP(3-)
Reactome.org link: R-HSA-8940100