PXD041505-3

PXD041505 is an original dataset announced via ProteomeXchange.

Title	beta 1 integrin signaling governs necroptosis via the chromatin remodeling factor CHD4
Description	Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. RIPK3, a key kinase mediating TNF-driven necroptosis signaling, is upregulated in fibrosis and contributes to the TNF-mediated inflammation. In bile duct ligation-induced liver fibrosis, we found that myofibroblasts are the major cell type expressing RIPK3. Genetic ablation of beta1 integrins, the major profibrotic ECM receptors in fibroblasts, not only abolished ECM fibrillogenesis but also blunted RIPK3 expression via an epigenetic mechanism mediated by the chromatin remodeling factor CHD4. While the function of CHD4 has been conventionally linked to NuRD and ChAHP complexes, we found that CHD4 potently repressed a set of genes, including Ripk3, with high locus specificity but independent of either the NuRD or ChAHP complex. Thus, our data uncover that beta1 integrin intrinsically links fibrotic signaling to RIPK3-driven inflammation via a novel mode of action of CHD4.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:13:39.877.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-13 01:39:40	ID requested
1	2023-10-30 15:22:44	announced
2	2023-11-14 08:30:02	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:13:40	announced	2024-10-22: Updated project metadata.

10.1016/J.CELREP.2023.113322;

submitter keyword: RIPK3, necroptosis,Integrin, inflammation, CHD4, fibrosis

Veit Hornung
contact affiliation	1. Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany 2. Research group Molecular Mechanisms of Inflammation, Max-Planck Institute of Biochemistry, Martinsried, Germany
contact email	hornung@genzentrum.lmu.de
lab head
Barbara Steigenberger
contact affiliation	MPI of Biochemistry
contact email	steigenberger@biochem.mpg.de
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/2023/10/PXD041505

PRIDE project URI

• PRIDE
  1. PXD041505
     1. Label: PRIDE project
     2. Name: beta 1 integrin signaling governs necroptosis via the chromatin remodeling factor CHD4