PXD038487

PXD038487 is an original dataset announced via ProteomeXchange.

Title	GID4-dependent proteome and interactome
Description	The CTLH complex is a multi-subunit ubiquitin ligase complex that recognizes substrates with Pro/N-degrons via substrate receptor GID4. Recently, focus has turned to the complex as a potential mediator of targeted protein degradation, but the role GID4-mediated substrate ubiquitylation and proteasomal degradation plays in humans has thus far remained unclear. Here, we report PFI-7, a potent, selective, and cell-active chemical probe that antagonizes Pro/N-degron binding to human GID4. Use of PFI-7 in proximity-dependent biotinylation enabled the identification of dozens of endogenous GID4-interacting proteins that bind via the GID4 substrate binding pocket, only a subset of which possess canonical Pro/N-degron sequences. GID4 interactors are enriched for nuclear and nucleolar proteins including RNA helicases. GID4 antagonism by PFI-7 altered protein levels of several proteins including RNA helicases as measured by label-free quantitative proteomics, defining proteins that are regulated by GID4 and the CTLH complex in humans. Interactions with GID4 via Pro/N-degron pathway were not sufficient to promote proteasomal degradation, however, demonstrating that CTLH interactors are regulated through a combination of degradative and non-degradative functions. The lack of degradation of GID4 interactors highlights potential challenges in utilizing GID4-recruiting bifunctional molecules for targeted protein degradation. Going forward, PFI-7 will be a valuable research tool for defining CTLH complex biology and honing targeted protein degradation strategies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:33.188.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Maitland
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-01 03:45:52	ID requested
1	2024-05-16 12:16:51	announced
⏵ 2	2024-10-22 06:39:33	announced	2024-10-22: Updated project metadata.

10.1038/S41589-024-01618-0;

submitter keyword: Human, BioID, LC-MS/MS

Cheryl H Arrowsmith
contact affiliation	Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario,Canada
contact email	cheryl.arrowsmith@uhnresearch.ca
lab head
Matthew Maitland
contact affiliation	University of Western Ontario
contact email	mmaitla2@uwo.ca
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/2024/05/PXD038487

PRIDE project URI

• PRIDE
  1. PXD038487
     1. Label: PRIDE project
     2. Name: GID4-dependent proteome and interactome