PXD051178 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Locking CBL in its native conformation presents a novel therapeutic opportunity in mutant CBL-dependent leukaemia (part 1) |
Description | Casitas B-lineage lymphoma (CBL) is critical to the negative regulation of receptor protein tyrosine kinases (RTKs). Mutant CBL can act as an adaptor and gain function to cause myeloproliferative diseases. Currently, there is no beneficial treatment available for leukaemia patients with CBL mutations. Using phage-display technique, we identified a peptide inhibitor CBLock that binds a pocket in CBL’s tyrosine kinase binding domain (TKBD) in its native conformation as revealed by a crystal structure. CBLock inhibits proliferation, causes cell cycle arrest and apoptosis in leukaemia cells that harbour CBL mutations. CBLock disrupts the interaction between CBL mutants and RTK/adaptor protein, hindering the gain-of-function of CBL mutants. We find reduced tumour progression and improved survival upon conditional expression of CBLock in a xenograft AML model. CBLock also resulted in reduced FLT3 downstream signalling. Therefore, inhibiting CBL-TKBD in its native state presents a useful therapeutic opportunity in targeting mutant/inactive CBL-dependent leukaemia. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-06 |
AnnouncementXML | Submission_2025-05-06_02:41:31.474.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: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-04-03 07:50:11 | ID requested | |
⏵ 1 | 2025-05-06 02:41:31 | announced | |
Publication List
Keyword List
submitter keyword: peptide inhibitor CBLock, CBL’s tyrosine kinase binding domain, leukaemia,Casitas B-lineage lymphoma (CBL) |
Contact List
Sara Rossana Zanivan |
contact affiliation | CRUK - Scotland Institute - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom |
contact email | Sara.Zanivan@glasgow.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
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD051178
- Label: PRIDE project
- Name: Locking CBL in its native conformation presents a novel therapeutic opportunity in mutant CBL-dependent leukaemia (part 1)