PXD043931-1

PXD043931 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-19 20:58:00	ID requested
⏵ 1	2023-07-19 20:58:13	announced

Dataset with its publication pending

submitter keyword: KRAS, SETD7, NSCLC, Protein methylation, Tumor suppressor

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

iProX dataset URI