PXD040671-1

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	2023-03-07
AnnouncementXML	Submission_2023-03-07_19:21:42.245.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.

Dataset with its publication pending

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