PXD043931
PXD043931 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Methylation of KRAS by SETD7 promotes KRAS degradation in non-small cell lung cancer |
Description | Oncogenic 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. |
HostingRepository | iProX |
AnnounceDate | 2023-07-19 |
AnnouncementXML | Submission_2023-07-19_20:58:13.062.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tian Xiao |
SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF-X |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2023-07-19 20:58:00 | ID requested | |
⏵ 1 | 2023-07-19 20:58:13 | announced |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: KRAS, SETD7, NSCLC, Protein methylation, Tumor suppressor |
Contact List
Tian Xiao | |
---|---|
contact affiliation | Shenzhen University |
contact email | txiao@szu.edu.cn |
lab head | |
Tian Xiao | |
contact affiliation | Shenzhen University |
contact email | txiao@szu.edu.cn |
dataset submitter |
Full Dataset Link List
iProX dataset URI |