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PXD043931

PXD043931 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMethylation of KRAS by SETD7 promotes KRAS degradation in non-small cell lung cancer
DescriptionOncogenic KRAS mutations are a key driver for initiation and progression in non-small-cell lung cancer (NSCLC). However, how post-translational modifications (PTMs) of KRAS, especially methylation, modify KRAS activity remain largely unclear. Here, we show that SET domain containing histone lysine methyltransferase 7 (SETD7) interacts with KRAS and methylates KRAS at lysines 182 and 184. SETD7-mediated methylation of KRAS leads to degradation of KRAS and attenuation of the RAS/MEK/ERK signaling cascade, endowing SETD7 with a potent tumor-suppressive role in NSCLC, both in vitro and in vivo. Mechanistically, RABGEF1, a ubiquitin E3 ligase of KRAS, was recruited and promoted KRAS degradation in a K182/K184 methylation-dependent manner. Notably, SETD7 is inversely correlated with KRAS at the protein level in clinical NSCLC tissues. Low SETD7 or RABGEF1 expression is associated with poor prognosis in lung adenocarcinoma patients. Altogether, our results elucidate a tumor-suppressive function of SETD7 that operates via modulating KRAS methylation and degradation.
HostingRepositoryiProX
AnnounceDate2023-07-19
AnnouncementXMLSubmission_2023-07-19_20:58:13.062.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTian Xiao
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-19 20:58:00ID requested
12023-07-19 20:58:13announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: KRAS, SETD7, NSCLC, Protein methylation, Tumor suppressor
Contact List
Tian Xiao
contact affiliationShenzhen University
contact emailtxiao@szu.edu.cn
lab head
Tian Xiao
contact affiliationShenzhen University
contact emailtxiao@szu.edu.cn
dataset submitter
Full Dataset Link List
iProX dataset URI