PXD071639 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | CBL ubiquitin ligase targets translation as a degrader E3 (part 2) |
| Description | Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional molecules that recruits an ubiquitin ligase (E3) and a neo-substrate into a ternary complex, enabling selective protein degradation. Despite the presence of over 600 E3s, only a handful are utilized in PROTAC application, potentially limiting the number of druggable targets. Here, we investigate whether Casitas B-cell lymphoma (CBL) can be harnessed as a degrader E3 to promote ubiquitination and degradation of the eukaryotic translation initiation factor 4E (eIF4E). Using a selective CBL binding peptide, CBLock, we demonstrate that CBL facilitates the ubiquitination of CBLock-eIF4E fusion both in vitro and in cells. We further developed peptidic PROTACs, termed eIFTerminators, by linking CBLock to an eIF4E-binding peptide. Among them, eIFTerminator4 was found to rapidly eliminate endogenous eIF4E via both lysosomal and proteasomal pathways. Additionally, eIF4E depletion was found to be associated with a reduction in eIF4A1 and eIF4G1 levels, thereby disrupting translation in cancer cells. Our findings establish proof-of-concept that CBL can function as a degrader E3, expanding the arsenal of E3s available for targeted protein degradation in combatting challenging drug targets. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-01-19 |
| AnnouncementXML | Submission_2026-01-18_16:17:43.039.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Sergio Lilla |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-12-05 07:10:48 | ID requested | |
| ⏵ 1 | 2026-01-18 16:17:44 | announced | |
Publication List
| Wicks AT, Buetow L, Suzuki T, Schmidt T, Lilla S, Macmillan-Jones A, Turney J, Gohlke A, Bushell M, Hock AK, Huang DT, CBL ubiquitin ligase targets translation as a degrader E3. Chem Sci, ():(2025) [pubmed] |
| 10.1039/d5sc06141e; |
Keyword List
| submitter keyword: CBL,PROTAC, Targeted protein Degradation, ubiquitin, mRNA, translation, eIF4E |
Contact List
| Danny Huang |
|---|
| contact affiliation | Cancer Research UK Scotland Institute (Formerly the Cancer Research UK Beatson Institute) Garscube Estate Switchback Road Bearsden Glasgow, G61 1BD |
| contact email | d.huang@crukscotlandinstitute.ac.uk |
| lab head | |
| Sergio Lilla |
|---|
| contact affiliation | Proteomics |
| contact email | s.lilla@beatson.gla.ac.uk |
| dataset submitter | |
Full Dataset Link List
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/2026/01/PXD071639 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD071639
- Label: PRIDE project
- Name: CBL ubiquitin ligase targets translation as a degrader E3 (part 2)
