PXD007876

PXD007876 is an original dataset announced via ProteomeXchange.

Title	AP-SWATH analysis reveals a direct involvement of VCP/p97 in integrated stress response signalling through CReP/PPP1R15B degradation
Description	The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of misfolded proteins in diverse cellular stress response pathways. Resolving the complexity of dynamic interactions with hosts of accessory proteins and substrates has therefore been a major challenge. Here, we used affinity-purification SWATH mass spectrometry (AP-SWATH) to identify proteins that specifically interact with a p97 substrate-trapping mutant, p97-E578Q. AP-SWATH identified differential interactions over a large detection range from abundant cofactors to pathway-specific partners and individual ligases such as RNF185 and MUL1 that were trapped in p97-E578Q complexes. In addition, we identified substrate candidates including the PP1 regulator CReP/PPP1R15B that dephosphorylates eIF2α and thus counteracts attenuation of translation by stress-kinases. We demonstrate here that p97 with its Ufd1-Npl4 adapter ensures rapid turnover and balanced levels of CReP in unperturbed cells. Moreover, we show that p97 is essential for the quantitative stress-induced degradation of CReP and, consequently, robust eIF2α phosphorylation to enforce the stress response. Thus, p97 not only facilitates bulk degradation of misfolded proteins upon stress, but also has an unanticipated function in directly modulating the integrated stress response at the level of signalling.
HostingRepository	PRIDE
AnnounceDate	2018-04-04
AnnouncementXML	Submission_2018-04-04_04:29:08.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ben Collins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-29 05:46:57	ID requested
⏵ 1	2018-04-04 04:29:09	announced

H, ü, lsmann J, Kravic B, Weith M, Gstaiger M, Aebersold R, Collins BC, Meyer H, AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response Signaling Through Facilitating CReP/PPP1R15B Degradation. Mol Cell Proteomics, 17(7):1295-1307(2018) [pubmed]

curator keyword: Biological

submitter keyword: p97, AP-SWATH, integrated stress response

Ben Collins
contact affiliation	Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland
contact email	collins@imsb.biol.ethz.ch
lab head
Ben Collins
contact affiliation	ETH Zurich
contact email	collins@imsb.biol.ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007876
     1. Label: PRIDE project
     2. Name: AP-SWATH analysis reveals a direct involvement of VCP/p97 in integrated stress response signalling through CReP/PPP1R15B degradation