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VCP–adaptor interactions are exceptionally dynamic and subject to differential modulation by a VCP inhibitor

ABSTRACT: In this study we use a combination of mass spectrometry-based proteomics and biophysical studies to characterize the interaction of adaptors with VCP. Our results reveal that most VCP–adaptor interactions are characterized by exceptionally rapid dynamics that in some cases are modulated by the VCP inhibitor NMS873. These findings have significant implications for both the regulation of VCP function and the impact of VCP inhibition on different VCP–adaptor complexes.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Liang Xue

LAB HEAD: Raymond Deshaies

PROVIDER: PXD004105 | Pride | 2016-07-18

REPOSITORIES: Pride

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Valosin-containing protein (VCP)-Adaptor Interactions are Exceptionally Dynamic and Subject to Differential Modulation by a VCP Inhibitor.

Xue Liang L Blythe Emily E EE Freiberger Elyse C EC Mamrosh Jennifer L JL Hebert Alexander S AS Reitsma Justin M JM Hess Sonja S Coon Joshua J JJ Deshaies Raymond J RJ

Molecular & cellular proteomics : MCP 20160712 9

Protein quality control (PQC) plays an important role in stemming neurodegenerative diseases and is essential for the growth of some cancers. Valosin-containing protein (VCP)/p97 plays a pivotal role in multiple PQC pathways by interacting with numerous adaptors that link VCP to specific PQC pathways and substrates and influence the post-translational modification state of substrates. However, our poor understanding of the specificity and architecture of the adaptors, and the dynamic properties ...[more]

PMID: 27406709

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