PXD052379 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development |
| Description | Cancers with activating mutations of KRAS show a high prevalence and poor prognosis but remain intractable, requiring innovative strategies to overcome the poor targetability of KRAS. Here, we report that KRAS expression was post-translationally up-regulated through the deubiquitination of KRAS protein when the scaffolding function of NDRG3 (N-Myc downstream regulated gene 3) promoted specific interaction between KRAS and a deubiquitinating enzyme, USP9X. In KRAS-mutant pancreatic or lung cancer cells KRAS protein expression, downstream signaling, and cell growth were highly dependent on NDRG3. In conditional KrasG12D knock-in mouse models of pancreatic ductal adenocarcinoma (PDAC), Ndrg3 depletion abolished Kras protein expression in pancreas, and suppressed pancreatic intraepithelial neoplasia (PanIN) formation. Mechanistically, KRAS protein bound to the C-terminal serine/threonine-rich region of NDRG3, subsequently going through the deubiquitination by USP9X recruited to the complex. This interaction could be disrupted in a dominant-negative manner by a C-terminal NDRG3 fragment that can bind KRAS but is defective in USP9X binding, highly suppressing the KRAS protein expression and KRAS-driven cell growth. In summary, KRAS-driven cancer development critically depends on the deubiquitination of KRAS protein mediated by USP9X/NDRG3, and KRAS-addicted cancers could be effectively targeted by inhibiting the KRAS-NDRG3 interaction. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-05-07 |
| AnnouncementXML | Submission_2025-05-06_17:01:28.013.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Sehoon Park |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
| ModificationList | phosphorylated residue |
| Instrument | LTQ |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2024-05-19 10:18:45 | ID requested | |
| ⏵ 1 | 2025-05-06 17:01:28 | announced | |
Publication List
| Koo H, Park KC, Sohn HA, Kang M, Kim DJ, Park ZY, Park S, Min SH, Park SH, You YM, Han Y, Kim BK, Lee CH, Kim YS, Chung SJ, Yeom YI, Lee DC, Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development. Nat Commun, 16(1):628(2025) [pubmed] |
| 10.1038/s41467-024-54476-8; |
Keyword List
| submitter keyword: KRAS protein deubiquitination |
| NDRG3 |
| USP9X |
| Pancreatic cancer |
Contact List
| Dong Chul Lee |
|---|
| contact affiliation | Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) |
| contact email | dclee@kribb.re.kr |
| lab head | |
| Sehoon Park |
|---|
| contact affiliation | GIST |
| contact email | sehoon94@gist.ac.kr |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052379
- Label: PRIDE project
- Name: Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development
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