Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.

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, to maintain vascular...

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Autores principales:	Siqi Gao, Matthew Menendez, Katarzyna Kurylowicz, Courtney T Griffin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dcbecacf4371497d9d497a8de5be278a
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spelling	oai:doaj.org-article:dcbecacf4371497d9d497a8de5be278a2021-12-02T20:10:19ZGenomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.1932-620310.1371/journal.pone.0253519https://doaj.org/article/dcbecacf4371497d9d497a8de5be278a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253519https://doaj.org/toc/1932-6203The 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, to 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-κB) signaling pathway components NFκB1 and IKBKG. We further verified that NFκB1 and IKBKG directly bind the Ripk3 promoter and prevent TNFα-induced Ripk3 transcription in cultured human primary endothelial cells. Moreover, NFκB1 prevents RIPK3-mediated death of primary endothelial cells. These data provide new insights into NF-κB signaling and Ripk3 transcriptional regulation in endothelial cells.Siqi GaoMatthew MenendezKatarzyna KurylowiczCourtney T GriffinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253519 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Siqi Gao Matthew Menendez Katarzyna Kurylowicz Courtney T Griffin Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 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, to 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-κB) signaling pathway components NFκB1 and IKBKG. We further verified that NFκB1 and IKBKG directly bind the Ripk3 promoter and prevent TNFα-induced Ripk3 transcription in cultured human primary endothelial cells. Moreover, NFκB1 prevents RIPK3-mediated death of primary endothelial cells. These data provide new insights into NF-κB signaling and Ripk3 transcriptional regulation in endothelial cells.
format	article
author	Siqi Gao Matthew Menendez Katarzyna Kurylowicz Courtney T Griffin
author_facet	Siqi Gao Matthew Menendez Katarzyna Kurylowicz Courtney T Griffin
author_sort	Siqi Gao
title	Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.
title_short	Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.
title_full	Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.
title_fullStr	Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.
title_full_unstemmed	Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.
title_sort	genomic locus proteomic screening identifies the nf-κb signaling pathway components nfκb1 and ikbkg as transcriptional regulators of ripk3 in endothelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/dcbecacf4371497d9d497a8de5be278a
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Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells.

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