PXD046139

PXD046139 is an original dataset announced via ProteomeXchange.

Title	Deubiquitinase JOSD2 promotes non-small cell lung cancer proliferation via deubiquitylation and inactivation of LKB1
Description	Deubiquitinases (DUBs), frequently overactivated in cancers, are associated with tumorigenesis and regarded as promising therapeutic targets. However, the underlying mechanism of DUBs promoting non-small cell lung cancer (NSCLC) are poorly understood. Through a global analysis of the contribution of 97 DUBs in NSCLC survival possibilities by The Cancer Genome Atlas (TCGA) database, we found that high expression of Josephin Domain-containing protein 2 (JOSD2) predicted the poor prognosis of patients. Depletion of JOSD2 significantly impeded NSCLC growth in vivo in both cell/patient-derived xenografts. Mechanistically, JOSD2 inhibits LKB1 kinase activity by removing K6-linked polyubiquitination, which was critical for maintaining LKB1-STRAD-MO25 complex integrity. Furthermore, we identified the first small molecule inhibitor of JOSD2 and the pharmacological inhibition of JOSD2 significantly arrested NSCLC proliferation in vitro/in vivo. Notably, our findings demonstrate a crucial role of JOSD2 in hindering LKB1 activity, highlighting JOSD2 as a potential therapeutic target in NSCLC and providing its inhibitors as a promising strategy for NSCLC treatment.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:20:36.792.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tao Yuan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-15 08:48:32	ID requested
⏵ 1	2024-01-26 06:20:37	announced

10.1038/s41392-023-01706-y;

Yuan T, Zeng C, Liu J, Zhao C, Ge F, Li Y, Qian M, Du J, Wang W, Li Y, Liu Y, Dai X, Zhou J, Chen X, Ma S, Zhu H, He Q, Yang B, Josephin domain containing 2 (JOSD2) promotes lung cancer by inhibiting LKB1 (Liver kinase B1) activity. Signal Transduct Target Ther, 9(1):11(2024) [pubmed]

submitter keyword: deubiquitinases, K6-linked polyubiquitination, non-small cell lung cancer, LKB1, kinase activity, JOSD2

Tao Yuan
contact affiliation	Zhejiang University,China
contact email	11919006@zju.edu.cn
lab head
Tao Yuan
contact affiliation	Zhejiang University
contact email	11919006@zju.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD046139

PRIDE project URI

• PRIDE
  1. PXD046139
     1. Label: PRIDE project
     2. Name: Deubiquitinase JOSD2 promotes non-small cell lung cancer proliferation via deubiquitylation and inactivation of LKB1