NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.

Optineurin is a ubiquitously expressed multifunctional cytoplasmic protein encoded by OPTN gene. The expression of optineurin is induced by various cytokines. Here we have investigated the molecular mechanisms which regulate optineurin gene expression and the relationship between optineurin and nucl...

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Autores principales:	Cherukuri Sudhakar, Ananthamurthy Nagabhushana, Nishant Jain, Ghanshyam Swarup
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9331527a054c4387b061acbbb712d35b
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spelling	oai:doaj.org-article:9331527a054c4387b061acbbb712d35b2021-11-25T06:16:20ZNF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.1932-620310.1371/journal.pone.0005114https://doaj.org/article/9331527a054c4387b061acbbb712d35b2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19340308/?tool=EBIhttps://doaj.org/toc/1932-6203Optineurin is a ubiquitously expressed multifunctional cytoplasmic protein encoded by OPTN gene. The expression of optineurin is induced by various cytokines. Here we have investigated the molecular mechanisms which regulate optineurin gene expression and the relationship between optineurin and nuclear factor kappaB (NF-kappaB). We cloned and characterized human optineurin promoter. Optineurin promoter was activated upon treatment of HeLa and A549 cells with tumor necrosis factor alpha (TNFalpha). Mutation of a putative NF-kappaB-binding site present in the core promoter resulted in loss of basal as well as TNFalpha-induced activity. Overexpression of p65 subunit of NF-kappaB activated this promoter through NF-kappaB site. Oligonucleotides corresponding to this putative NF-kappaB-binding site showed binding to NF-kappaB. TNFalpha-induced optineurin promoter activity was inhibited by expression of inhibitor of NF-kappaB (IkappaBalpha) super-repressor. Blocking of NF-kappaB activation resulted in inhibition of TNFalpha-induced optineurin gene expression. Overexpressed optineurin partly inhibited TNFalpha-induced NF-kappaB activation in Hela cells. Downregulation of optineurin by shRNA resulted in an increase in TNFalpha-induced as well as basal NF-kappaB activity. These results show that optineurin promoter activity and gene expression are regulated by NF-kappaB pathway in response to TNFalpha. In addition these results suggest that there is a negative feedback loop in which TNFalpha-induced NF-kappaB activity mediates expression of optineurin, which itself functions as a negative regulator of NF-kappaB.Cherukuri SudhakarAnanthamurthy NagabhushanaNishant JainGhanshyam SwarupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5114 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cherukuri Sudhakar Ananthamurthy Nagabhushana Nishant Jain Ghanshyam Swarup NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.
description	Optineurin is a ubiquitously expressed multifunctional cytoplasmic protein encoded by OPTN gene. The expression of optineurin is induced by various cytokines. Here we have investigated the molecular mechanisms which regulate optineurin gene expression and the relationship between optineurin and nuclear factor kappaB (NF-kappaB). We cloned and characterized human optineurin promoter. Optineurin promoter was activated upon treatment of HeLa and A549 cells with tumor necrosis factor alpha (TNFalpha). Mutation of a putative NF-kappaB-binding site present in the core promoter resulted in loss of basal as well as TNFalpha-induced activity. Overexpression of p65 subunit of NF-kappaB activated this promoter through NF-kappaB site. Oligonucleotides corresponding to this putative NF-kappaB-binding site showed binding to NF-kappaB. TNFalpha-induced optineurin promoter activity was inhibited by expression of inhibitor of NF-kappaB (IkappaBalpha) super-repressor. Blocking of NF-kappaB activation resulted in inhibition of TNFalpha-induced optineurin gene expression. Overexpressed optineurin partly inhibited TNFalpha-induced NF-kappaB activation in Hela cells. Downregulation of optineurin by shRNA resulted in an increase in TNFalpha-induced as well as basal NF-kappaB activity. These results show that optineurin promoter activity and gene expression are regulated by NF-kappaB pathway in response to TNFalpha. In addition these results suggest that there is a negative feedback loop in which TNFalpha-induced NF-kappaB activity mediates expression of optineurin, which itself functions as a negative regulator of NF-kappaB.
format	article
author	Cherukuri Sudhakar Ananthamurthy Nagabhushana Nishant Jain Ghanshyam Swarup
author_facet	Cherukuri Sudhakar Ananthamurthy Nagabhushana Nishant Jain Ghanshyam Swarup
author_sort	Cherukuri Sudhakar
title	NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.
title_short	NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.
title_full	NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.
title_fullStr	NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.
title_full_unstemmed	NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.
title_sort	nf-kappab mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of nf-kappab.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/9331527a054c4387b061acbbb712d35b
work_keys_str_mv	AT cherukurisudhakar nfkappabmediatestumornecrosisfactoralphainducedexpressionofoptineurinanegativeregulatorofnfkappab AT ananthamurthynagabhushana nfkappabmediatestumornecrosisfactoralphainducedexpressionofoptineurinanegativeregulatorofnfkappab AT nishantjain nfkappabmediatestumornecrosisfactoralphainducedexpressionofoptineurinanegativeregulatorofnfkappab AT ghanshyamswarup nfkappabmediatestumornecrosisfactoralphainducedexpressionofoptineurinanegativeregulatorofnfkappab
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NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB.

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