PXD021305

PXD021305 is an original dataset announced via ProteomeXchange.

Title	The inflammasome-activated cytokine IL-1 is targeted for ubiquitylation and proteasomal degradation to limit its inflammatory potential
Description	Interleukin-1B (IL-1B) is pathologically activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in wide-spread diseases. Therefore, IL-1B activity must be fine-tuned to enable anti-microbial responses whilst limiting collateral damage. Here we report that, relative to other inflammasome components, IL-1B is rapidly turned over by the proteasome and this correlates with its decoration by K11-, K63- and K48-linked ubiquitin chains. This IL-1 degradation signal is not only a feature of inflammasome priming but is also triggered upon inflammasome activation. We demonstrate that IL-1 K133 is modified by ubiquitin and forms a salt bridge with IL-1B D129. Loss of IL-1 K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1Bprotein levels. Accordingly, IL-1B K133R/K133R mice display increased precursor IL-1Bupon inflammasome priming and increased bioactive IL-1B following inflammasome activation, both in vitro and following LPS injection in vivo. These findings reveal new mechanisms for limiting IL-1B activity and safeguarding against damaging inflammation.
HostingRepository	PRIDE
AnnounceDate	2021-04-01
AnnouncementXML	Submission_2021-05-28_06:10:35.854.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Dagley
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-04 02:50:06	ID requested
1	2021-03-31 20:14:19	announced
⏵ 2	2021-05-28 06:10:36	announced	2021-05-28: Updated publication reference for PubMed record(s): 33976225.

Vijayaraj SL, Feltham R, Rashidi M, Frank D, Liu Z, Simpson DS, Ebert G, Vince A, Herold MJ, Kueh A, Pearson JS, Dagley LF, Murphy JM, Webb AI, Lawlor KE, Vince JE, limits its cleavage by caspase-1 and targets it for proteasomal degradation. Nat Commun, 12(1):2713(2021) [pubmed]

submitter keyword: Interleukin-1, inflammasome, caspase-1, caspase-8, ubiquitin, proteasome, Toll-like receptor, inflammation

James Vince
contact affiliation	Laboratory Head Vince Laboratory The Walter and Eliza Hall Institute Victoria, Australia 3052
contact email	vince@wehi.edu.au
lab head
Laura Dagley
contact affiliation	WEHI
contact email	dagley.l@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/2021/04/PXD021305

PRIDE project URI

• PRIDE
  1. PXD021305
     1. Label: PRIDE project
     2. Name: The inflammasome-activated cytokine IL-1 is targeted for ubiquitylation and proteasomal degradation to limit its inflammatory potential