PXD054126-1

PXD054126 is an original dataset announced via ProteomeXchange.

Title	FDA-approved Disulfiram Inhibits the NLRP3 Inflammasome
Description	The NLRP3 inflammasome is dysregulated in autoinflammatory disorders caused by inherited mutations and contributes to the pathogenesis of several chronic inflammatory diseases. In this study, we discovered that disulfiram, a safe FDA-approved drug, specifically inhibits the NLRP3 inflammasome, but not the NLRC4 or AIM2 inflammasomes. Disulfiram suppresses caspase-1 activation, ASC speck formation, and pyroptosis induced by several stimuli that activate NLRP3. Mechanistically, NLRP3 is palmitoylated at cysteine 126, a modification required for its localization to the trans-Golgi network and inflammasome activation which was inhibited by disulfiram. Administration of disulfiram to animals inhibited the NLRP3, but not the NLRC4 inflammasome in vivo. Our study uncovers a mechanism by which disulfiram targets NLRP3 and provides a rationale for using a safe FDA-approved drug for the treatment of NLRP3-associated inflammatory diseases.
HostingRepository	PRIDE
AnnounceDate	2024-07-25
AnnouncementXML	Submission_2024-07-25_09:37:12.136.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jie Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-22 19:24:59	ID requested
⏵ 1	2024-07-25 09:37:12	announced

Dataset with its publication pending

submitter keyword: gasdermin D, inflammasome,disulfiram

Jie Xu
contact affiliation	University of Michigan
contact email	biojiexu@yahoo.com
lab head
Jie Xu
contact affiliation	University of Michigan
contact email	biojiexu@yahoo.com
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/2024/07/PXD054126

PRIDE project URI

• PRIDE
  1. PXD054126
     1. Label: PRIDE project
     2. Name: FDA-approved Disulfiram Inhibits the NLRP3 Inflammasome