A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development.
Eukaryotic cells have evolved signaling pathways that help to restore cellular homeostasis in response to various physiological or pathological conditions. ATF4 is a transcription factor whose mRNA translation is stimulated in response to stress-activated eIF2alpha kinases. Established conditions th...
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doaj-3ac1ea0d423b4e0a98013adceca4aed32020-11-25T00:27:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012679510.1371/journal.pone.0126795A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development.Kwonyoon KangHyung Don RyooJung-Eun ParkJee-Hyun YoonMin-Ji KangEukaryotic cells have evolved signaling pathways that help to restore cellular homeostasis in response to various physiological or pathological conditions. ATF4 is a transcription factor whose mRNA translation is stimulated in response to stress-activated eIF2alpha kinases. Established conditions that activate eIF2alpha phosphorylation and ATF4 translation include excessive stress in the endoplasmic reticulum (ER) and amino acid deprivation. ATF4 is activated through a unique translational activation mechanism that involves multiple upstream open reading frames (uORFs) in the 5'-untranslated region (UTR), which is conserved from yeast to mammals. Taking advantage of this, we developed a translational activation reporter of ATF4 in Drosophila, in which the dsRed reporter coding sequence was placed downstream of the Drosophila ATF4 5' UTR. This reporter remained inactive in most tissues under normal conditions, but showed dsRed expression when starved, or when challenged with conditions that imposed ER stress. In normally developing flies, a small number of cell types showed reporter expression even without exogenous stress, which included the salivary gland, gut, the male reproductive organ, and the photoreceptor cells, suggestive of inherent stress during the normal development of these cell types. These results establish a new tool to study ATF4-mediated stress response in Drosophila development and disease.http://europepmc.org/articles/PMC4433282?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kwonyoon Kang Hyung Don Ryoo Jung-Eun Park Jee-Hyun Yoon Min-Ji Kang |
spellingShingle |
Kwonyoon Kang Hyung Don Ryoo Jung-Eun Park Jee-Hyun Yoon Min-Ji Kang A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development. PLoS ONE |
author_facet |
Kwonyoon Kang Hyung Don Ryoo Jung-Eun Park Jee-Hyun Yoon Min-Ji Kang |
author_sort |
Kwonyoon Kang |
title |
A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development. |
title_short |
A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development. |
title_full |
A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development. |
title_fullStr |
A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development. |
title_full_unstemmed |
A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development. |
title_sort |
drosophila reporter for the translational activation of atf4 marks stressed cells during development. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
Eukaryotic cells have evolved signaling pathways that help to restore cellular homeostasis in response to various physiological or pathological conditions. ATF4 is a transcription factor whose mRNA translation is stimulated in response to stress-activated eIF2alpha kinases. Established conditions that activate eIF2alpha phosphorylation and ATF4 translation include excessive stress in the endoplasmic reticulum (ER) and amino acid deprivation. ATF4 is activated through a unique translational activation mechanism that involves multiple upstream open reading frames (uORFs) in the 5'-untranslated region (UTR), which is conserved from yeast to mammals. Taking advantage of this, we developed a translational activation reporter of ATF4 in Drosophila, in which the dsRed reporter coding sequence was placed downstream of the Drosophila ATF4 5' UTR. This reporter remained inactive in most tissues under normal conditions, but showed dsRed expression when starved, or when challenged with conditions that imposed ER stress. In normally developing flies, a small number of cell types showed reporter expression even without exogenous stress, which included the salivary gland, gut, the male reproductive organ, and the photoreceptor cells, suggestive of inherent stress during the normal development of these cell types. These results establish a new tool to study ATF4-mediated stress response in Drosophila development and disease. |
url |
http://europepmc.org/articles/PMC4433282?pdf=render |
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