PXD025675

PXD025675 is an original dataset announced via ProteomeXchange.

Title	Genomic locus proteomic screening identifies the NF-kB signaling pathway components NFkB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells
Description	The receptor-interacting protein kinase 3 (RIPK3) is a multi-functional protein best known for facilitating cellular necroptosis and inflammation. Recent evidence from our lab indicates that RIPK3 expression must be tightly regulated in endothelial cells to promote angiogenesis and maintain vascular integrity during embryogenesis and to provide protection from postnatal atherosclerosis. RIPK3 activity and stability are regulated by post-translational modifications and caspase-dependent cleavage. However, less is known about the transcriptional regulation of Ripk3. Here we utilized an unbiased CRISPR-based technology called genomic locus proteomics (GLoPro) to screen transcription factors and coregulatory proteins associated with the Ripk3 locus in a murine endothelial cell line. We found that 41 nuclear proteins are specifically enriched at the Ripk3 locus, including the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway components NFkB1 and IKBKG. We further verified that NFkB1 and IKBKG directly bind the Ripk3 promoter and prevent TNFa-induced Ripk3 transcription in cultured human primary endothelial cells. Moreover, NFkB1 prevents RIPK3-mediated death of primary endothelial cells. These data provide new insights into NF-kB signaling and Ripk3 transcriptional regulation in endothelial cells.
HostingRepository	PRIDE
AnnounceDate	2021-06-09
AnnouncementXML	Submission_2021-06-09_14:41:28.597.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Siqi Gao
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-27 22:38:29	ID requested
⏵ 1	2021-06-09 14:41:28	announced

Dataset with its publication pending

submitter keyword: GLoPro

Courtney Griffin
contact affiliation	Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, US
contact email	courtney-griffin@omrf.org
lab head
Siqi Gao
contact affiliation	University of Pennsylvania
contact email	siqi.gao@pennmedicine.upenn.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025675
     1. Label: PRIDE project
     2. Name: Genomic locus proteomic screening identifies the NF-kB signaling pathway components NFkB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells