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Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after...

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Autores principales: Yang, Yujie, Chan, William K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279416/
https://www.ncbi.nlm.nih.gov/pubmed/32414129
http://dx.doi.org/10.3390/ijms21103449
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author Yang, Yujie
Chan, William K.
author_facet Yang, Yujie
Chan, William K.
author_sort Yang, Yujie
collection PubMed
description The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation of autophagy by short-term nutrition deprivation reduces its levels. Treatment of chloroquine retards the degradation of AHR and triggers physical interaction between AHR and LC3B. Knockdown of LC3B suppresses the chloroquine-mediated increase of AHR. Down-regulation of p23 promotes AHR degradation via autophagy with no change of the autophagy-related gene expression. Although most data in this study were derived from HeLa cells, human lung (A549), liver (Hep3B), and breast (T-47D and MDA-MB-468) cells also exhibit AHR levels sensitive to chloroquine treatment and AHR–p62/LC3 interactions. Here we provide evidence supporting that AHR undergoes the p62/LC3-mediated selective autophagy in HeLa cells.
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spelling pubmed-72794162020-06-17 Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone Yang, Yujie Chan, William K. Int J Mol Sci Article The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation of autophagy by short-term nutrition deprivation reduces its levels. Treatment of chloroquine retards the degradation of AHR and triggers physical interaction between AHR and LC3B. Knockdown of LC3B suppresses the chloroquine-mediated increase of AHR. Down-regulation of p23 promotes AHR degradation via autophagy with no change of the autophagy-related gene expression. Although most data in this study were derived from HeLa cells, human lung (A549), liver (Hep3B), and breast (T-47D and MDA-MB-468) cells also exhibit AHR levels sensitive to chloroquine treatment and AHR–p62/LC3 interactions. Here we provide evidence supporting that AHR undergoes the p62/LC3-mediated selective autophagy in HeLa cells. MDPI 2020-05-13 /pmc/articles/PMC7279416/ /pubmed/32414129 http://dx.doi.org/10.3390/ijms21103449 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Yujie
Chan, William K.
Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
title Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
title_full Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
title_fullStr Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
title_full_unstemmed Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
title_short Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
title_sort selective autophagy maintains the aryl hydrocarbon receptor levels in hela cells: a mechanism that is dependent on the p23 co-chaperone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279416/
https://www.ncbi.nlm.nih.gov/pubmed/32414129
http://dx.doi.org/10.3390/ijms21103449
work_keys_str_mv AT yangyujie selectiveautophagymaintainsthearylhydrocarbonreceptorlevelsinhelacellsamechanismthatisdependentonthep23cochaperone
AT chanwilliamk selectiveautophagymaintainsthearylhydrocarbonreceptorlevelsinhelacellsamechanismthatisdependentonthep23cochaperone