PXD045860

PXD045860 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in hepatic stellate cells
Description	Liver injury causes “transdifferentiation” of quiescent hepatic stellate cells (Q-HSCs) into wound repairing myofibroblasts (MF-HSCs), whose uncontrolled activation leads ultimately to liver fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, using a compendium of in vitro, ex vivo and in vivo models of fibrogenic liver injuries in addition to human liver samples, we report that O-linked β D N acetylglucosaminylation (O GlcNAcylation), a post-translational modification (PTM) considered as nutritional sensor, is increased during myofibroblastic activation of HSCs and is required for their pro-fibrotic activities. Mechanistically, a multi omics approach combining proteomic, epigenomic and transcriptomic data mining revealed that O GlcNAcylation controls the transcriptional program of MF-HSCs by targeting the key fibrogenic transcription factors Basonuclin 2 (BNC2) and TEA domain transcription factor 4 (TEAD4) together with the Yes associated protein 1 (YAP1) co-activator. Indeed, inhibition of protein O GlcNAcylation impedes their stability leading to decreased functionality of the BNC2/TEAD4/YAP1 complex towards promoting activation of fibrogenic transcriptional regulatory elements. Altogether, this study unravels the fibrogenic role of protein O-GlcNAcylation identifying a vulnerable regulatory process in activated HSCs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:58.476.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	BRAY FABRICE
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-02 08:33:36	ID requested
1	2024-05-21 08:20:41	announced
⏵ 2	2024-10-22 06:39:58	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: fibrogenic liver injuries, human, O-linked β D N acetylglucosaminylation

Fabrice BRay
contact affiliation	Miniaturization for Synthesis, Analysis & Proteomics, UAR 3290, CNRS, University of Lille, 59655 Villeneuve d’Ascq Cedex, France
contact email	fabrice.bray@univ-lille.fr
lab head
BRAY FABRICE
contact affiliation	MSAP USR 3290
contact email	fabrice.bray@univ-lille.fr
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/2024/05/PXD045860

PRIDE project URI

• PRIDE
  1. PXD045860
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in hepatic stellate cells