PXD043565

PXD043565 is an original dataset announced via ProteomeXchange.

Title	VCF1 is a p97 cofactor promoting recruitment of p97-UFD1-NPL4 to ubiquitylated substrates
Description	The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is directed to ubiquitylated client proteins via multiple cofactors, most of which interact with the p97 N-domain. Here, we discovered that FAM104A, a protein of unknown function that we named VCF1, acts as a novel p97 cofactor in human cells. Detailed structure-function studies revealed that VCF1 directly binds p97 via a conserved novel alpha-helical motif that recognizes the p97 N-domain with unusually high affinity exceeding that of other cofactors. We show that VCF1 engages in joint p97 complex formation with the heterodimeric primary p97 cofactor UFD1-NPL4 and promotes p97-UFD1-NPL4-dependent proteasomal degradation of ubiquitylated substrates in cells. Mechanistically, VCF1 stimulates the affinity of the p97-UFD1-NPL4 complex for ubiquitin conjugates indirectly via its binding to p97 but does not itself interact with ubiquitin. Collectively, our findings establish VCF1 as an unconventional p97 cofactor that promotes p97-dependent protein turnover by facilitating p97-UFD1-NPL4 recruitment to ubiquitylated targets.
HostingRepository	PRIDE
AnnounceDate	2024-03-14
AnnouncementXML	Submission_2024-03-14_04:14:06.244.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Mund
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-05 12:05:58	ID requested
⏵ 1	2024-03-14 04:14:06	announced

10.1038/S41467-024-46760-4;

submitter keyword: AP-MS

Andreas Mund
contact affiliation	Universisity of Copehangen, Novo Nordisk Foundation Center for Protein Research
contact email	andreas.mund@cpr.ku.dk
lab head
Andreas Mund
contact affiliation	University of Copenhagen
contact email	andreas.mund@cpr.ku.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/03/PXD043565

PRIDE project URI

• PRIDE
  1. PXD043565
     1. Label: PRIDE project
     2. Name: VCF1 is a p97 cofactor promoting recruitment of p97-UFD1-NPL4 to ubiquitylated substrates