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The transcription factor Xrp1 is required for PERK-mediated antioxidant gene induction in Drosophila

The transcription factor Xrp1 is required for PERK-mediated antioxidant gene induction in Drosophila

Authors :
Brian Brown
Sahana Mitra
Finnegan D Roach
Deepika Vasudevan
Hyung Don Ryoo
Source :
eLife, Vol 10 (2021)
Publication Year :
2021
Publisher :
eLife Sciences Publications Ltd, 2021.

Abstract

PERK is an endoplasmic reticulum (ER) transmembrane sensor that phosphorylates eIF2α to initiate the Unfolded Protein Response (UPR). eIF2α phosphorylation promotes stress-responsive gene expression most notably through the transcription factor ATF4 that contains a regulatory 5’ leader. Possible PERK effectors other than ATF4 remain poorly understood. Here, we report that the bZIP transcription factor Xrp1 is required for ATF4-independent PERK signaling. Cell-type-specific gene expression profiling in Drosophila indicated that delta-family glutathione-S-transferases (gstD) are prominently induced by the UPR-activating transgene Rh1G69D. Perk was necessary and sufficient for such gstD induction, but ATF4 was not required. Instead, Perk and other regulators of eIF2α phosphorylation regulated Xrp1 protein levels to induce gstDs. The Xrp1 5’ leader has a conserved upstream Open Reading Frame (uORF) analogous to those that regulate ATF4 translation. The gstD-GFP reporter induction required putative Xrp1 binding sites. These results indicate that antioxidant genes are highly induced by a previously unrecognized UPR signaling axis consisting of PERK and Xrp1.

Details

Language :
English
ISSN :
2050084X
Volume :
10
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.3871a8bb819e4fc58256c93679f7d1b9
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.74047