PXD027196-1

PXD027196 is an original dataset announced via ProteomeXchange.

Title	CD95/Fas suppresses NF-B activation through recruitment of KPC2 in a CD95L/FasL-independent mechanism
Description	CD95 expression is preserved in triple-negative breast cancers (TNBCs) and CD95 loss in these cells triggers the induction of a pro-inflammatory program promoting the recruitment of cytotoxic NK cells impairing tumor growth. Herein, we identify a novel interaction partner of CD95, Kip1 ubiquitination-promoting complex protein 2 (KPC2) using an unbiased proteomic approach. Independently of CD95L, CD95/KPC2 interaction contributes to the partial degradation of p105 (NFκB1) and the subsequent generation of p50 homodimers, which transcriptionally represses NF-κB-driven gene expression. Mechanistically, KPC2 interacts with the C-terminal region of CD95 and serves as an adaptor to recruit RelA (p65) and KPC1, which acts as E3 ubiquitin-protein ligase promoting the degradation of p105 into p50. Loss of CD95 in TNBC cells releases KPC2, limiting the formation of the NF-κB inhibitory homodimer complex (p50/p50), promoting NF-κB activation and the production of pro-inflammatory cytokines, that could account for the immune landscape remodeling in TNBC cells
HostingRepository	PRIDE
AnnounceDate	2021-12-06
AnnouncementXML	Submission_2021-12-06_06:34:28.471.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luc Negroni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-08 09:10:49	ID requested
⏵ 1	2021-12-06 06:34:28	announced

Dataset with its publication pending

submitter keyword: Fas, KPC2, p65, NF-kappaB, inflammation

Patrick Legembre
contact affiliation	CRIBL, Université Limoges, Limoges, France.
contact email	patrick.legembre@inserm.fr
lab head
Luc Negroni
contact affiliation	CNRS
contact email	luc.negroni@igbmc.fr
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/2021/12/PXD027196

PRIDE project URI

• PRIDE
  1. PXD027196
     1. Label: PRIDE project
     2. Name: CD95/Fas suppresses NF-B activation through recruitment of KPC2 in a CD95L/FasL-independent mechanism