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PXD062101

PXD062101 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMapping the Interactome of KRAS and Its G12C/D/V Mutants by Integrating TurboID Proximity Labeling with Quantitative Proteomics
DescriptionRAS is one of the most frequently mutated proto-oncogenes in human malignancies, with mutation sites and subtypes exhibiting tumor-type dependent distribution. Oncogenic RAS mutations will maintain continuously GTP-bound activation states that leading to dysregulation of downstream signaling, ultimately disrupting cellular homeostasis to induce malignant transformation of cells. In this study, we employed TurboID proximity-labeling technology integrated with quantitative proteomics LC-MS/MS to systematically characterize the proximal binding proteins of wild-type KRAS and three high-frequency oncogenic mutant subtypes G12C, G12D and G12V. Through comprehensive bioinformatic analysis of mutation-specific interaction networks and distinct metabolic pathways, we identified significant enrichment of mutant KRAS binding proteins in insulin signaling pathway, reactive oxygen species related pathways, glucose and lipid metabolism and so on. Metabolic reprogramming pathways in KRAS G12 mutations collectively fuel tumor proliferation and immune evasion. In addition, we also comparatively analyzed the proximal binding proteins similarity in three G12 mutants. Notably, we observed that the KRAS E3 ubiquitin ligase adaptor LZTR1 diminished binding with mutations, and the mTORC1 important regulatory protein LAMTOR1 was enhanced recruitment by mutations. This multi-dimensional profiling delineates a comprehensive mapping of KRAS WT and G12 mutant interactomes and unveils the metabolic reprogramming pathways associated with KRAS activating mutations. Our analysis result provides potential therapeutic targets for KRAS-driven tumorigenesis while establishing a mechanistic framework for developing KRAS mutation-specific therapeutic strategies.
HostingRepositoryPRIDE
AnnounceDate2025-06-09
AnnouncementXMLSubmission_2025-06-08_16:11:32.210.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterchengzhi wang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentZenoTOF 7600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-03-21 01:13:24ID requested
12025-06-08 16:11:33announced
Publication List
10.3390/biology14050477;
Song J, Wang B, Zou M, Zhou H, Ding Y, Ren W, Fang L, Zhang J, Mapping the Interactome of KRAS and Its G12C/D/V Mutants by Integrating TurboID Proximity Labeling with Quantitative Proteomics. Biology (Basel), 14(5):(2025) [pubmed]
Keyword List
submitter keyword: KRAS interactome
KRAS G12 mutants
TurboID proximity-labeling
Quantitative Proteomics;Metabolic reprogramming
Contact List
Lei Fang
contact affiliationState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing 210093, China.
contact emailnjfanglei@nju.edu.cn
lab head
chengzhi wang
contact affiliationuniversity
contact email602022350046@smail.nju.edu.cn
dataset submitter
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Dataset FTP location
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