PXD068486 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Interactomics analysis of SLAP in colorectal cancer cells |
| Description | The mechanistic target of rapamycin complex 2 (mTORC2) signaling pathway, which regulates cell growth and migration, exhibits oncogenic function in colorectal cancer (CRC). mTORC2 signaling is primarily activated by a complex assembly of mTOR, RICTOR, SIN1, and mLST8, but how dysregulation of this mechanism contributes to its oncogenic function remains elusive. Here, we show that the Src-Like Adaptor Protein (SLAP), a negative regulator of tyrosine kinase signaling receptors, controls mTORC2 integrity to mediate its tumor-suppressive function in CRC. Mechanistically, SLAP interacts with mLST8 and facilitates its non-degradative ubiquitination at lysines 86 and 215, thereby reducing mTORC2 integrity and mTORC2-AKT signaling. The E3 ubiquitin ligase UBE3C was identified as a novel SLAP interactor involved in this ubiquitination process. Functionally, SLAP inhibition of CRC cell growth and invasion was dependent upon mTORC2 signaling inhibition. In immunodeficient mice CRC xenografts, SLAP depletion enhanced mTORC2 activity and sensitized CRC cells to mTOR catalytic inhibitors. Together, our findings reveal a previously unrecognized SLAP–UBE3C–mLST8 axis that regulates mTORC2 integrity and suggest a potential therapeutic avenue for targeting mTORC2 in CRC. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-03-11 |
| AnnouncementXML | Submission_2026-03-11_03:01:55.558.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD068486 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Functional Proteomics Platform FPP |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | 6x(13)C; 6x(13)C; iodoacetamide derivatized residue |
| Instrument | LTQ Orbitrap XL; LTQ Orbitrap Elite |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-09-18 06:08:42 | ID requested | |
| ⏵ 1 | 2026-03-11 03:01:56 | announced | |
Publication List
| 10.6019/PXD068486; |
| Mevizou R, Naim D, Cauchois F, Naudin C, Greaves G, Espie K, Felipe B, Simon V, Boublik Y, Nguyen J, Urbach S, Roche S, Sirvent A, SLAP controls mTORC2 integrity via UBE3C-mediated non-degradative mLST8 ubiquitination to suppress colorectal tumorigenesis. Cell Death Differ, ():(2025) [pubmed] |
| 10.1038/s41418-025-01633-1; |
Keyword List
| submitter keyword: Human, cancer, SILAC, colon |
Contact List
| Serge ROCHE |
|---|
| contact affiliation | CRBM institute, UMR5237 CNRS, France |
| contact email | Serge.roche@crbm.cnrs.fr |
| lab head | |
| Functional Proteomics Platform FPP |
|---|
| contact affiliation | FPP CNRS |
| contact email | contact@fpp.cnrs.fr |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD068486
- Label: PRIDE project
- Name: Interactomics analysis of SLAP in colorectal cancer cells
