PXD026533

PXD026533 is an original dataset announced via ProteomeXchange.

Title	Ubiquitylation of RIPK3 beyond-the-RHIM limits RIPK3 activity and cell death
Description	Pathogen recognition receptors and TNF superfamily members engage Receptor Interacting Serine/threonine Kinase-3 (RIPK3) to activate programmed cell death, including MLKL-mediated necroptosis and caspase-8-dependent apoptosis. However, the post-translational control of RIPK3 signalling is not fully understood. Using mass-spectrometry, we identified a novel ubiquitylation site on murine RIPK3 beyond the RIP homotypic interaction motif (RHIM) on K469. Complementation of RIPK3-deficient cells with a Ripk3K469R mutant demonstrated that the decoration of RIPK3 K469 by ubiquitin limits both RIPK3-mediated caspase-8 activation and apoptotic killing, in addition to RIPK3 autophosphorylation and MLKL-mediated necroptosis. Unexpectedly, the overall ubiquitylation of mutant RIPK3K469R was enhanced, which largely resulted from additional RIPK3 ubiquitylation on K359. Loss of RIPK3 K359 ubiquitylation reduced RIPK3K469R hyper-ubiquitylation and limited the ability of Ripk3K469R/K469R to trigger enhanced killing. Ripk3K469R/K469R mice challenged with Salmonella displayed increased bacterial loads in the spleen and liver, with reduced IFN serum levels. Therefore, RIPK3 K469 ubiquitylation can function to prevent RIPK3 ubiquitylation on alternate lysine residues, which otherwise promote RIPK3 oligomerization and consequent cell death signalling.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_03:03:54.691.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrod Sandow
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue
Instrument	timsTOF Pro; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-07 06:07:02	ID requested
⏵ 1	2022-08-12 03:03:55	announced

Frank D, Garnish SE, Sandow JJ, Weir A, Liu L, Clayer E, Meza L, Rashidi M, Cobbold SA, Scutts SR, Doerflinger M, Anderton H, Lawlor KE, Lalaoui N, Kueh AJ, Eng VV, Ambrose RL, Herold MJ, Samson AL, Feltham R, Murphy JM, Ebert G, Pearson JS, Vince JE, Ubiquitylation of RIPK3 beyond-the-RHIM can limit RIPK3 activity and cell death. iScience, 25(7):104632(2022) [pubmed]

submitter keyword: necroptosis, apoptosis, cell death, RIPK3, MLKL, caspase-8, ubiquitin

James Vince
contact affiliation	The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3052, Australia
contact email	vince@wehi.edu.au
lab head
Jarrod Sandow
contact affiliation	WEHI
contact email	sandow@wehi.edu.au
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/2022/08/PXD026533

PRIDE project URI

• PRIDE
  1. PXD026533
     1. Label: PRIDE project
     2. Name: Ubiquitylation of RIPK3 beyond-the-RHIM limits RIPK3 activity and cell death