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NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways

Autophagy is an evolutionally conserved process that recycles aged or damaged intracellular components through a lysosome-dependent pathway. Although this multistep process is propagated in the cytoplasm by the orchestrated activity of the mTOR complex, phosphatidylinositol 3-kinase, and a set of au...

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Autores principales: Cho, Young-Eun, Kim, Yong-Jun, Lee, Sun, Park, Jae-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430719/
https://www.ncbi.nlm.nih.gov/pubmed/34502226
http://dx.doi.org/10.3390/ijms22179318
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author Cho, Young-Eun
Kim, Yong-Jun
Lee, Sun
Park, Jae-Hoon
author_facet Cho, Young-Eun
Kim, Yong-Jun
Lee, Sun
Park, Jae-Hoon
author_sort Cho, Young-Eun
collection PubMed
description Autophagy is an evolutionally conserved process that recycles aged or damaged intracellular components through a lysosome-dependent pathway. Although this multistep process is propagated in the cytoplasm by the orchestrated activity of the mTOR complex, phosphatidylinositol 3-kinase, and a set of autophagy-related proteins (ATGs), recent investigations have suggested that autophagy is tightly regulated by nuclear events. Thus, it is conceivable that the nucleolus, as a stress-sensing and -responding intranuclear organelle, plays a role in autophagy regulation, but much is unknown concerning the nucleolar controls in autophagy. In this report, we show a novel nucleolar–cytoplasmic axis that regulates the cytoplasmic autophagy process: nucleolar protein NOP53 regulates the autophagic flux through two divergent pathways, the ZKSCAN3-dependent and -independent pathways. In the ZKSCAN3-dependent pathway, NOP53 transcriptionally activates a master autophagy suppressor ZKSCAN3, thereby inhibiting MAP1LC3B/LC3B induction and autophagy propagation. In the ZKSCAN3-independent pathway, NOP53 physically interacts with histone H3 to dephosphorylate S10 of H3, which, in turn, transcriptionally downregulates the ATG7 and ATG12 expressions. Our results identify nucleolar protein NOP53 as an upstream regulator of the autophagy process.
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spelling pubmed-84307192021-09-11 NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways Cho, Young-Eun Kim, Yong-Jun Lee, Sun Park, Jae-Hoon Int J Mol Sci Article Autophagy is an evolutionally conserved process that recycles aged or damaged intracellular components through a lysosome-dependent pathway. Although this multistep process is propagated in the cytoplasm by the orchestrated activity of the mTOR complex, phosphatidylinositol 3-kinase, and a set of autophagy-related proteins (ATGs), recent investigations have suggested that autophagy is tightly regulated by nuclear events. Thus, it is conceivable that the nucleolus, as a stress-sensing and -responding intranuclear organelle, plays a role in autophagy regulation, but much is unknown concerning the nucleolar controls in autophagy. In this report, we show a novel nucleolar–cytoplasmic axis that regulates the cytoplasmic autophagy process: nucleolar protein NOP53 regulates the autophagic flux through two divergent pathways, the ZKSCAN3-dependent and -independent pathways. In the ZKSCAN3-dependent pathway, NOP53 transcriptionally activates a master autophagy suppressor ZKSCAN3, thereby inhibiting MAP1LC3B/LC3B induction and autophagy propagation. In the ZKSCAN3-independent pathway, NOP53 physically interacts with histone H3 to dephosphorylate S10 of H3, which, in turn, transcriptionally downregulates the ATG7 and ATG12 expressions. Our results identify nucleolar protein NOP53 as an upstream regulator of the autophagy process. MDPI 2021-08-27 /pmc/articles/PMC8430719/ /pubmed/34502226 http://dx.doi.org/10.3390/ijms22179318 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cho, Young-Eun
Kim, Yong-Jun
Lee, Sun
Park, Jae-Hoon
NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways
title NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways
title_full NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways
title_fullStr NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways
title_full_unstemmed NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways
title_short NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways
title_sort nop53 suppresses autophagy through zkscan3-dependent and -independent pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430719/
https://www.ncbi.nlm.nih.gov/pubmed/34502226
http://dx.doi.org/10.3390/ijms22179318
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