PXD045485-1

PXD045485 is an original dataset announced via ProteomeXchange.

Title	GMPS promoting tumor immune evasion by regulating the glycosylation modification of PD-L1
Description	Hepatocellular carcinoma (HCC) is a malignant tumor characterized by rapid progression, whose development is attributed to severe immune evasion. Here, we conducted proteomic and scRNA-Seq analysis on advanced HCC tissues and identified a significant molecule, Guanine monophosphate synthase (GMPS). We found that GMPS was closely associated with the immune evasion of HCC. Further investigation revealed that GMPS increased PD-L1 expression by regulating its ubiquitination and glycosylation modification. Mechanistically, GMPS enhanced the bond between PD-L1 and the catalytic subunit STT3A of oligosaccharyltransferase (OST) through acting as an additional module connecting the Sec61 channel complex and STT3A, which aided in the translocation and modification of nascent peptides. The increased PD-L1 impaired the tumor-killing function of CD8+ T cells, ultimately leading to immune evasion. Importantly, targeting GMPS with angustmycin A, an inhibitor of GMPS activity, significantly suppressed PD-L1 expression and tumor growth in HCC, which also increased sensitivity to anti-CTLA-4 immunotherapy. These findings suggested the potential of targeting GMPS as a promising therapeutic approach for HCC.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:12:50.720.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinyu Guo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	(18)O label at both C-terminal oxygens
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-19 05:27:41	ID requested
⏵ 1	2026-05-24 16:12:51	announced

10.1038/s41418-024-01432-0;

Guo X, Cui T, Sun L, Fu Y, Cheng C, Wu C, Zhu Y, Liang S, Liu Y, Zhou S, Li X, Ji C, Ma K, Zhang N, Chu Q, Xing C, Deng S, Wang J, Liu Y, Liu L, A STT3A-dependent PD-L1 glycosylation modification mediated by GMPS drives tumor immune evasion in hepatocellular carcinoma. Cell Death Differ, 32(5):944-958(2025) [pubmed]

submitter keyword: PTM,HCC, PD-L1, Immunotherapy

Xinyu Guo
contact affiliation	The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China; The First Affiliated Hospital of Harbin Medical University
contact email	2427887530@qq.com
lab head
Xinyu Guo
contact affiliation	The First Affiliated Hospital of Harbin Medical University
contact email	2427887530@qq.com
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/2026/05/PXD045485

PRIDE project URI

• PRIDE
  1. PXD045485
     1. Label: PRIDE project
     2. Name: GMPS promoting tumor immune evasion by regulating the glycosylation modification of PD-L1