Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor

Abstract Selective autophagy requires the autophagy receptor specifically localizing to the target for degradation. In the budding yeast, Atg39 and Atg40 function as an autophagy receptor for the endoplasmic reticulum (ER)-selective autophagy, referred to as ER-phagy. The expression level of the ATG...

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Autores principales: Tomoaki Mizuno, Kenji Irie
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/ae17bae1d330441cb721ee616540c5eb
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spelling oai:doaj.org-article:ae17bae1d330441cb721ee616540c5eb2021-12-02T17:30:40ZMsn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor10.1038/s41598-021-91480-02045-2322https://doaj.org/article/ae17bae1d330441cb721ee616540c5eb2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91480-0https://doaj.org/toc/2045-2322Abstract Selective autophagy requires the autophagy receptor specifically localizing to the target for degradation. In the budding yeast, Atg39 and Atg40 function as an autophagy receptor for the endoplasmic reticulum (ER)-selective autophagy, referred to as ER-phagy. The expression level of the ATG39 gene is increased in response to ER stress and nitrogen starvation. Under unstressed conditions, ATG39 transcription is repressed by Mig1/2 repressors. ER stress activates Snf1 AMP-activated protein kinase (AMPK), which negatively regulates Mig1/2 and consequently derepresses ATG39 transcription. However, ATG39 expression is still induced by ER stress and nitrogen starvation in the absence of Snf1, suggesting that additional molecules are involved in regulation of ATG39 expression. Here, we identify Msn2/4 transcription factors as an activator of ATG39 transcription. Not only ATG39 promoter activity but also ER-phagy are downregulated by loss of Msn2/4 and disruption of Msn2/4-binding consensus sequences located in the ATG39 promoter. We also find that the cAMP-dependent protein kinase pathway is involved in Msn2/4-mediated transcriptional regulation of ATG39. Our results suggest that yeast ER-phagy is appropriately controlled through modulation of the expression level of the ER-phagy receptor involving multiple signaling pathways and transcription factors.Tomoaki MizunoKenji IrieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tomoaki Mizuno
Kenji Irie
Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor
description Abstract Selective autophagy requires the autophagy receptor specifically localizing to the target for degradation. In the budding yeast, Atg39 and Atg40 function as an autophagy receptor for the endoplasmic reticulum (ER)-selective autophagy, referred to as ER-phagy. The expression level of the ATG39 gene is increased in response to ER stress and nitrogen starvation. Under unstressed conditions, ATG39 transcription is repressed by Mig1/2 repressors. ER stress activates Snf1 AMP-activated protein kinase (AMPK), which negatively regulates Mig1/2 and consequently derepresses ATG39 transcription. However, ATG39 expression is still induced by ER stress and nitrogen starvation in the absence of Snf1, suggesting that additional molecules are involved in regulation of ATG39 expression. Here, we identify Msn2/4 transcription factors as an activator of ATG39 transcription. Not only ATG39 promoter activity but also ER-phagy are downregulated by loss of Msn2/4 and disruption of Msn2/4-binding consensus sequences located in the ATG39 promoter. We also find that the cAMP-dependent protein kinase pathway is involved in Msn2/4-mediated transcriptional regulation of ATG39. Our results suggest that yeast ER-phagy is appropriately controlled through modulation of the expression level of the ER-phagy receptor involving multiple signaling pathways and transcription factors.
format article
author Tomoaki Mizuno
Kenji Irie
author_facet Tomoaki Mizuno
Kenji Irie
author_sort Tomoaki Mizuno
title Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor
title_short Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor
title_full Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor
title_fullStr Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor
title_full_unstemmed Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor
title_sort msn2/4 transcription factors positively regulate expression of atg39 er-phagy receptor
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/ae17bae1d330441cb721ee616540c5eb
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