PXD014097-1

PXD014097 is an original dataset announced via ProteomeXchange.

Title	Auto-phosphorylation at serine 166 regulates RIP kinase 1 mediated cell death and inflammation
Description	Receptor interacting kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 and other receptors, and has been implicated in the pathogenesis of inflammatory and degenerative diseases. RIPK1 kinase activity induces cell death by activating apoptosis and necroptosis, however the mechanisms and phosphorylation events regulating RIPK1-dependent cell death signalling remain poorly understood. Here we show that RIPK1 auto-phosphorylation at serine (S) 166 plays a critical role for the activation of RIPK1 kinase-dependent apoptosis and necroptosis. Moreover, we show that S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis of inflammatory pathologies in vivo in four relevant mouse models. Mechanistically, we provide evidence that trans auto-phosphorylation at S166 modulates RIPK1 kinase activation but is not by itself sufficient for the induction of cell death. These results show that S166 auto-phosphorylation licences RIPK1 kinase activity to induce downstream cell death signalling and inflammation, suggesting that S166 phosphorylation can serve as a reliable biomarker for RIPK1 kinase-dependent pathologies.
HostingRepository	PRIDE
AnnounceDate	2020-03-23
AnnouncementXML	Submission_2020-03-23_02:33:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Janica Wiederstein
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-03 05:31:45	ID requested
⏵ 1	2020-03-23 02:33:54	announced
2	2020-04-14 02:57:31	announced	2020-04-14: Updated publication reference for PubMed record(s): 32269263.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Cell death, inflammation, Phosphorylation

Manolis Pasparakis
contact affiliation	Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
contact email	pasparakis@uni-koeln.de
lab head
Janica Wiederstein
contact affiliation	Institute for Genetics/CECAD (AG Krüger)
contact email	jwieders@uni-koeln.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/2020/03/PXD014097

PRIDE project URI

• PRIDE
  1. PXD014097
     1. Label: PRIDE project
     2. Name: Auto-phosphorylation at serine 166 regulates RIP kinase 1 mediated cell death and inflammation