⮝ Full datasets listing
PXD081878
PXD081878 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Phosphorylation Protects Oncogenic RAS from LZTR1-Mediated Degradation |
| Description | Oncogenic KRAS and NRAS mutations are common in hematologic malignancies, but how they signal in that context is less well characterized than in carcinomas. To uncover novel RAS biology and potential therapeutic vulnerabilities, we employed a multi-omics screening approach in multiple myeloma to identify regulators of RAS activity. We report that the phosphatase PP1C dephosphorylates the conserved T148 residue on RAS, which in turn permits LZTR1-dependent proteasomal degradation. Notably, LZTR1 is ineffective against KRAS A146 gain-of-function mutations, which are adjacent to T148 and enriched in hematologic cancers, such as diffuse large B cell lymphoma and acute myeloid leukemia. Remarkably, we find that KRAS protein is four-fold less stable in hematologic versus carcinoma cells, offering a unique therapeutic opportunity targeting RAS protein stability mechanisms. The kinases PAK1 and PAK2 were shown to shield RAS from LZTR1-dependent degradation by phosphorylating T148, and targeting PAK1/2 activity improved RAS-directed therapy. Collectively, our findings reveal a regulatory circuit governing RAS stability that is preferentially active in blood cancers and potentially druggable. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-07-30 |
| AnnouncementXML | Submission_2026-07-30_01:14:34.074.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Bj�rn H�upl |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl; Acetyl |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-07-29 12:30:14 | ID requested | |
| ⏵ 1 | 2026-07-30 01:14:34 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Oncogenic RAS, Hematologic Cancers, BioID2 interactome, DatasetType:Proteomics |
Contact List
| Ryan M. Young | |
|---|---|
| contact affiliation | National Institutes of Health |
| contact email | youngrm@nih.gov |
| lab head | |
| Bj�rn H�upl | |
| contact affiliation | DKFZ/DKTK |
| contact email | b.haeupl@dkfz-heidelberg.de |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive-ftp.ucsd.edu/v14/MSV000102658/ |
