PXD038830

PXD038830 is an original dataset announced via ProteomeXchange.

Title	Deciphering the clinical significance and kinase functions of GSK3α in colon cancer by proteomics and phosphoproteomics
Description	In this study, paired tumors and distant normal tissues (DNTs) collected from 78 treatment-naïve colon cancer patients were subjected to tandem mass tag (TMT)-based proteomics. We found that the expression of GSK3α, but not GSK3β, was significantly correlated with the overall survival (OS) of colon cancer patients in 3 independent cohorts. To decipher the roles of GSK3α in colon cancer, we profiled the phosphorylation substrates of GSK3α. Initial in vitro and in vivo phosphoproteomics analyses uncovered 156 phosphosites from 130 proteins specifically regulated by GSK3α but not GSK3β. Notably, the levels of some phosphosites, including HSF1S303p, CANXS583p, MCM2S41p, POGZS425p, SRRM2T983p and PRPF4BS431p, were significantly correlated with the OS of colon cancer patients. Further pull-down assays identified 23 proteins, such as THRAP3, BCLAF1 and STAU1, that showed strong binding affinity to GSK3α. The tight interaction between THRAP3 and GSK3α was verified by biochemical experiments. Notably, among the 18 phosphosites of THRAP3, phosphorylation at S248, S253 and S682 is specifically mediated by GSK3α in vitro and in cell lines. Mutation of S248 to D (S248D), which mimics the effect of phosphorylation, obviously increased cancer cell migration and the binding affinity to proteins related to DNA damage repair. Collectively, this work not only discloses the specific function of GSK3α as a kinase but also suggests GSK3α as a promising therapeutic target for colon cancer.
HostingRepository	iProX
AnnounceDate	2023-03-03
AnnouncementXML	Submission_2023-05-22_00:45:50.753.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Li Gao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus; Orbitrap Exploris 480; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-14 17:13:19	ID requested
⏵ 1	2023-05-22 00:45:51	announced

Gao L, Lu Y, Chen HN, Li Z, Hu M, Zhang R, Wang X, Xu Z, Gong Y, Wang R, Du D, Hai S, Li S, Su D, Li Y, Xu H, Zhou ZG, Dai L, in Colon Cancer by Proteomics and Phosphoproteomics. Mol Cell Proteomics, 22(5):100545(2023) [pubmed]

submitter keyword: proteomics, phosphoproteomics, GSK3α, THRAP3, colon cancer

Lunzhi Dai
contact affiliation	State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
contact email	lunzhi.dai@scu.edu.cn
lab head
Li Gao
contact affiliation	Sichuan University
contact email	865842052@qq.com
dataset submitter

iProX dataset URI