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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8430719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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