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PXD025675-1

PXD025675 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGenomic locus proteomic screening identifies the NF-kB signaling pathway components NFkB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2021-06-09
AnnouncementXMLSubmission_2021-06-09_14:41:28.597.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSiqi Gao
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListbiotinylated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-27 22:38:29ID requested
12021-06-09 14:41:28announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: GLoPro
Contact List
Courtney Griffin
contact affiliationCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, US
contact emailcourtney-griffin@omrf.org
lab head
Siqi Gao
contact affiliationUniversity of Pennsylvania
contact emailsiqi.gao@pennmedicine.upenn.edu
dataset submitter
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Dataset FTP location
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