PXD055877

PXD055877 is an original dataset announced via ProteomeXchange.

Title	Changes in Cereblon substrates landscape upon molecular glue treatment
Description	The specificity of the ubiquitination process is mediated by the E3 ligases. Discriminating specific substrates of E3s from interacting proteins is one of the major challenges in the field. We previously developed BioE3, a biotin-based approach that uses BirA-E3 fusions together with ubiquitin fused to a low-affinity AviTag to obtain a site-specific and proximity-dependent biotinylation of the target proteins. We proved the suitability of BioE3 to identify targets of RING and HECT-type E3 ligases. Here we demonstrate that the system is suitable for the multi-protein complex Cullin-RING E3s, choosing as proof of principle the substrate receptor CRBN. We identified both CRBN endogenous substrates and new neosubstrates upon pomalidomide treatment, including CSDE1 which contains a new motif involved in the binding to CRBN in presence of pomalidomide. Importantly, we observed a major rearrangement of the endogenous ubiquitination landscape upon this molecular glue treatment. The ability of our system to detect changes in the specificity of the E3s in response to drugs may be of interest in the development of targeted protein degradation strategies.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_02:56:10.727.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-16 00:57:42	ID requested
⏵ 1	2025-05-07 02:56:11	announced

Merino-Cacho L, Barroso-Gomila O, Pozo-Rodr, í, guez M, Muratore V, Guinea-P, é, rez C, Serrano Á, P, é, rez C, Cano-L, ó, pez S, Urcullu A, Azkargorta M, Iloro I, Galdeano C, Ju, á, rez-Jim, é, nez J, Mayor U, Elortza F, Barrio R, Sutherland JD, Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome. Cell Commun Signal, 23(1):101(2025) [pubmed]

10.1186/s12964-025-02091-5;

submitter keyword: Ubiquitination, cereblon, bioE3

Felix Elortza
contact affiliation	Proteomics Platform CIC bioGUNE Bzkaia Tech. Park Build. 800 Derio 48160 Bizkaia (Spain)
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
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/2025/05/PXD055877

PRIDE project URI

• PRIDE
  1. PXD055877
     1. Label: PRIDE project
     2. Name: Changes in Cereblon substrates landscape upon molecular glue treatment