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Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6? 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 ATF6? as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6? 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 ATF6? target genes. Mechanistically, exposure of cells to NaSal results in ATF6? trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6?, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses.

SUBMITTER: Mugge FLB 

PROVIDER: S-EPMC5569067 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Mügge Fernanda L B FLB   Silva Aristóbolo M AM  

Scientific reports 20170823 1


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 activit  ...[more]

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