Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells

Reactive oxygen species are now widely recognized as important players contributing both to cell homeostasis and the development of disease. In this respect nitric oxide (NO) is no exception. The discussion here will center on regulation of the inducible form of nitric oxide synthase (iNOS) for two...

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Autores principales:	FELLEY-BOSCO,EMANUELA, BENDER,FLORENT, QUEST,ANDREW F.G.
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2002
Materias:	inducible nitric oxide synthase proteosome_mediated proteolysis nitroxysomes cytokines caveolae caveolin-1
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200007
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spelling	oai:scielo:S0716-976020020002000072002-12-26Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cellsFELLEY-BOSCO,EMANUELABENDER,FLORENTQUEST,ANDREW F.G. inducible nitric oxide synthase proteosome_mediated proteolysis nitroxysomes cytokines caveolae caveolin-1 Reactive oxygen species are now widely recognized as important players contributing both to cell homeostasis and the development of disease. In this respect nitric oxide (NO) is no exception. The discussion here will center on regulation of the inducible form of nitric oxide synthase (iNOS) for two reasons. First, only iNOS produces micromolar NO concentrations, amounts that are high by comparison with the picomolar to nanomolar concentrations resulting from Ca2+-controlled NO production by endothelial eNOS or neuronal nNOS. Second, iNOS is not constitutively expressed in cells and regulation of this isoenzyme, in contrast to endothelial eNOS or neuronal nNOS, is widely considered to occur at the transcriptional level only. In particular, we were interested in the possibility that caveolin-1, a protein that functions as a tumor suppressor in colon carcinoma cells (Bender et al., 2002; this issue), might regulate iNOS activity. Our results provide evidence for the existence of a post-transcriptional mechanism controlling iNOS protein levels that involves caveolin-1-dependent sequestration of iNOS within a detergent-insoluble compartment. Interestingly, despite the high degree of conservation of the caveolin-1 scaffolding domain binding motif within all NOS enzymes, the interaction detected between caveolin-1 and iNOS in vitro is crucially dependent on presence of a caveolin-1 sequence element immediately adjacent to the scaffolding domain. A model is presented summarizing the salient aspects of these results. These observations are important in the context of tumor biology, since down-regulation of caveolin-1 is predicted to promote uncontrolled iNOS activity, genotoxic damage and thereby facilitate tumor development in humansinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.35 n.2 20022002-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200007en10.4067/S0716-97602002000200007
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	inducible nitric oxide synthase proteosome_mediated proteolysis nitroxysomes cytokines caveolae caveolin-1
spellingShingle	inducible nitric oxide synthase proteosome_mediated proteolysis nitroxysomes cytokines caveolae caveolin-1 FELLEY-BOSCO,EMANUELA BENDER,FLORENT QUEST,ANDREW F.G. Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
description	Reactive oxygen species are now widely recognized as important players contributing both to cell homeostasis and the development of disease. In this respect nitric oxide (NO) is no exception. The discussion here will center on regulation of the inducible form of nitric oxide synthase (iNOS) for two reasons. First, only iNOS produces micromolar NO concentrations, amounts that are high by comparison with the picomolar to nanomolar concentrations resulting from Ca2+-controlled NO production by endothelial eNOS or neuronal nNOS. Second, iNOS is not constitutively expressed in cells and regulation of this isoenzyme, in contrast to endothelial eNOS or neuronal nNOS, is widely considered to occur at the transcriptional level only. In particular, we were interested in the possibility that caveolin-1, a protein that functions as a tumor suppressor in colon carcinoma cells (Bender et al., 2002; this issue), might regulate iNOS activity. Our results provide evidence for the existence of a post-transcriptional mechanism controlling iNOS protein levels that involves caveolin-1-dependent sequestration of iNOS within a detergent-insoluble compartment. Interestingly, despite the high degree of conservation of the caveolin-1 scaffolding domain binding motif within all NOS enzymes, the interaction detected between caveolin-1 and iNOS in vitro is crucially dependent on presence of a caveolin-1 sequence element immediately adjacent to the scaffolding domain. A model is presented summarizing the salient aspects of these results. These observations are important in the context of tumor biology, since down-regulation of caveolin-1 is predicted to promote uncontrolled iNOS activity, genotoxic damage and thereby facilitate tumor development in humans
author	FELLEY-BOSCO,EMANUELA BENDER,FLORENT QUEST,ANDREW F.G.
author_facet	FELLEY-BOSCO,EMANUELA BENDER,FLORENT QUEST,ANDREW F.G.
author_sort	FELLEY-BOSCO,EMANUELA
title	Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
title_short	Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
title_full	Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
title_fullStr	Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
title_full_unstemmed	Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
title_sort	caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells
publisher	Sociedad de Biología de Chile
publishDate	2002
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200007
work_keys_str_mv	AT felleyboscoemanuela caveolin1mediatedposttranscriptionalregulationofinduciblenitricoxidesynthaseinhumancoloncarcinomacells AT benderflorent caveolin1mediatedposttranscriptionalregulationofinduciblenitricoxidesynthaseinhumancoloncarcinomacells AT questandrewfg caveolin1mediatedposttranscriptionalregulationofinduciblenitricoxidesynthaseinhumancoloncarcinomacells
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Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells

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