Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes

Abstract In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium s...

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Autores principales:	Fernanda L. B. Mügge, Aristóbolo M. Silva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/164de12006754a55bab72c7f91a0b1a6
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spelling	oai:doaj.org-article:164de12006754a55bab72c7f91a0b1a62021-12-02T15:05:23ZAspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes10.1038/s41598-017-09500-x2045-2322https://doaj.org/article/164de12006754a55bab72c7f91a0b1a62017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09500-xhttps://doaj.org/toc/2045-2322Abstract In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6α mRNA and protein levels, but these events are not accompanied by ATF6 activation. Conversely, NaSal inhibited ATF6 transactivating activity elicited by various ER stress-inducing stimuli in different cell types. This resulted in reduced expression of a subset of ATF6α target genes. Mechanistically, exposure of cells to NaSal results in ATF6α trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6α, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses.Fernanda L. B. MüggeAristóbolo M. SilvaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fernanda L. B. Mügge Aristóbolo M. Silva Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
description	Abstract In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6α mRNA and protein levels, but these events are not accompanied by ATF6 activation. Conversely, NaSal inhibited ATF6 transactivating activity elicited by various ER stress-inducing stimuli in different cell types. This resulted in reduced expression of a subset of ATF6α target genes. Mechanistically, exposure of cells to NaSal results in ATF6α trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6α, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses.
format	article
author	Fernanda L. B. Mügge Aristóbolo M. Silva
author_facet	Fernanda L. B. Mügge Aristóbolo M. Silva
author_sort	Fernanda L. B. Mügge
title	Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
title_short	Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
title_full	Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
title_fullStr	Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
title_full_unstemmed	Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
title_sort	aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of atf6α and downstream target genes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/164de12006754a55bab72c7f91a0b1a6
work_keys_str_mv	AT fernandalbmugge aspirinmetabolitesodiumsalicylateselectivelyinhibitstranscriptionalactivityofatf6aanddownstreamtargetgenes AT aristobolomsilva aspirinmetabolitesodiumsalicylateselectivelyinhibitstranscriptionalactivityofatf6aanddownstreamtargetgenes
_version_	1718388815320580096

Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes

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