PXD015047

PXD015047 is an original dataset announced via ProteomeXchange.

Title	DPP9 activity and not protein binding inhibits the CARD8 inflammasome
Description	Inflammasomes are multiprotein complexes formed in response to pathogens. NLRP1 and CARD8 are related proteins that form inflammasomes, but the pathogen-associated signal(s) and the molecular mechanisms controlling their activation have not been established. Inhibitors of the serine dipeptidyl peptidases DPP8 and DPP9 (DPP8/9) were recently discovered to activate both NLRP1 and CARD8. Interestingly, DPP9 binds directly to NLRP1 and CARD8, and this interaction, in addition to DPP9’s catalytic activity, may contribute to the inhibition of NLRP1. Here, we use activity-based probes, reconstituted inflammasome assays, and mass spectrometry-based proteomics to further investigate the DPP9-CARD8 interaction. We show that the DPP9-CARD8 interaction, unlike the DPP9-NLRP1 interaction, is not disrupted by DPP9 inhibitors or mutations that block autoproteolysis. Moreover, wild-type, but not catalytically-inactive mutant, DPP9 rescues CARD8-mediated cell death in DPP9 knockout cells. Together, this work reveals DPP9 activity and not direct protein binding restrains the CARD8 inflammasome, and suggests the binding interaction likely serves some other biological purpose.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:57:44.934.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Griswold
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-16 01:10:51	ID requested
1	2019-10-23 06:57:44	announced
2	2019-10-25 04:09:27	announced	2019-10-25: Updated publication reference for PubMed record(s): 31525884.
⏵ 3	2024-10-22 04:57:50	announced	2024-10-22: Updated project metadata.

10.1021/acschembio.9b00462;

Griswold AR, Ball DP, Bhattacharjee A, Chui AJ, Rao SD, Taabazuing CY, Bachovchin DA, DPP9's Enzymatic Activity and Not Its Binding to CARD8 Inhibits Inflammasome Activation. ACS Chem Biol, 14(11):2424-2429(2019) [pubmed]

submitter keyword: Val-boroPro, CARD8,DPP9

Daniel Bachovchin
contact affiliation	Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
contact email	bachovcd@mskcc.org
lab head
Andrew Griswold
contact affiliation	Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, New York, USA.
contact email	ang2055@med.cornell.edu
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/2019/10/PXD015047

PRIDE project URI

• PRIDE
  1. PXD015047
     1. Label: PRIDE project
     2. Name: DPP9 activity and not protein binding inhibits the CARD8 inflammasome