PXD040671

PXD040671 is an original dataset announced via ProteomeXchange.

Title	ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy
Description	The programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases for regulating PD-1 stability have been reported, deubiquitinase (DUB) governing PD-1 homeostasis to modulate tumor immunotherapy remains unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1. Mechanistically, USP5 interacts with PD-1, leading to deubiquitination and stabilization of PD-1. Moreover, extracellular signal-regulated kinase (ERK) phosphorylates PD-1 at Thr234 and stabilizes PD-1 through promoting PD-1/USP5 interaction. Conditional knockout (cKO) of Usp5 in T cells significantly suppresses tumor growth in mice largely through decreasing PD-1 and increasing tumor-infiltrating cytotoxic CD8+ T cells. Furthermore, co-targeting USP5 and ERK signaling has an additive effect on reducing PD-1 and suppressing tumor growth in vivo. Together, this study uncovers the molecular mechanism for ERK/USP5 axis in regulating PD-1 stability and identifies potential combined therapeutic strategies for enhancing anti-tumor efficacy.
HostingRepository	iProX
AnnounceDate	2023-03-17
AnnouncementXML	Submission_2023-05-22_00:46:48.779.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiangling 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	2023-03-07 19:21:24	ID requested
1	2023-03-07 19:21:42	announced
⏵ 2	2023-05-22 00:46:49	announced	2023-05-22: Update publication information.

Xiao X, Shi J, He C, Bu X, Sun Y, Gao M, Xiang B, Xiong W, Dai P, Mao Q, Xing X, Yao Y, Yu H, Xu G, Li S, Ren Y, Chen B, Jiang C, Meng G, Lee YR, Wei W, Freeman GJ, Xie C, Zhang J, ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy. Nat Commun, 14(1):2859(2023) [pubmed]

submitter keyword: PD-1, USP5, Tumor Immunotherapy, Ubiquitination, Phosphorylation

Jingfang Zhang
contact affiliation	Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University
contact email	jinfang_zhang@whu.edu.cn
lab head
Xiangling Xiao
contact affiliation	Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University
contact email	xiaoxiangling@whu.edu.cn
dataset submitter

iProX dataset URI