PXD045862

PXD045862 is an original dataset announced via ProteomeXchange.

Title	Proximity proteomics reveals UCH-L1 as an essential regulator of NLRP3-mediated IL-1β production in human macrophages and microglia
Description	Activation of the NACHT, LRR family pyrin domain containing 3 (NLRP3) inflammasome complex is an essential innate immune signalling mechanism. To reveal how NLRP3 inflammasome assembly and activation are controlled, in particular by components of the ubiquitin system, proximity labelling, affinity purification and RNAi screening approaches were performed. Our study provides an intricate time-resolved molecular map of different phases of NLRP3 inflammasome activation. We discovered that ubiquitin C-terminal hydrolase 1 (UCH-L1) interacts with the NACHT domain of NLRP3, and downregulation of UCH-L1 decreases pro-IL-1β levels. UCH-L1 chemical inhibition with small molecules interfered with NLRP3 puncta formation and ASC oligomerisation, leading to altered IL-1β cleavage and secretion, particularly in microglia cells, which exhibited elevated UCH-L1 expression as compared to monocytes/macrophages. Altogether, we profiled NLRP3 inflammasome activation dynamics and highlight UCH-L1 as an important modulator of NLRP3-mediated IL-1β production, suggesting that a pharmacological inhibitor of UCH-L1 may decrease inflammation-associated pathologies.
HostingRepository	PRIDE
AnnounceDate	2024-04-24
AnnouncementXML	Submission_2024-04-24_07:15:03.422.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhu Liang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-02 10:01:42	ID requested
⏵ 1	2024-04-24 07:15:03	announced

Dataset with its publication pending

submitter keyword: Affinity purification-mass spectrometry,APEX2 proximity labelling, NLRP3 inflammasome

Benedikt Kessler
contact affiliation	Nuffield Department of Medicine, University of Oxford
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Zhu Liang
contact affiliation	University of Oxford
contact email	charles.zhu.liang@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045862
     1. Label: PRIDE project
     2. Name: Proximity proteomics reveals UCH-L1 as an essential regulator of NLRP3-mediated IL-1β production in human macrophages and microglia