Document Type

Article

Publication Title

International Journal of Molecular Sciences

ISSN

1422-0067

Volume

21

Issue

10

DOI

10.3390/ijms21103449

First Page

3449

Publication Date

5-13-2020

Abstract

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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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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