{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:55:03Z","timestamp":1790916903581,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R15ES023104"],"award-info":[{"award-number":["R15ES023104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which involves a myriad of cellular functions ranging from xenobiotic sensing in the liver to immune response modulation. Discovery of endogenous tryptophan metabolites as ligands of this receptor allows us to understand the roles of AHR in cell growth and immune responses, making this receptor an attractive target for treatment of cancer and autoimmune diseases. Much emphasis has been focused on the involvement of AHR in cellular functions; however, mechanisms that affect the cellular expression of this receptor are poorly understood. Historically, our knowledge of AHR has been primarily acquired from the mouse Hepa1c1c7 hepatoma cells because this receptor is robustly expressed and functional in these cells. Since AHR is also active in human liver, human hepatoma cell lines such as Hep3B and HepG2 have been widely used to study AHR function. In this paper, we investigate how the AHR protein levels are maintained in these hepatoma cells. We provide mechanistic insights into the regulation of AHR expression using the HaloTag fusion of mouse AHR, together with two-dimensional (2D) monolayer and three-dimensional (3D) spheroid culture models. In summary, we prove that AHR is continuously degraded by proteasomal degradation without exogenous ligands in hepatoma monolayer and spheroids. AHR in mouse Hepa1c1c7, but not human Hep3B and HepG2, cells also undergo lysosomal degradation to a lesser extent. Inhibition of proteasomal degradation blocks the degradation and synthesis of the AHR protein.<\/jats:p>","DOI":"10.3390\/ijms27188369","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:23:56Z","timestamp":1790864636000},"page":"8369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights into Regulation of the Aryl Hydrocarbon Receptor Expression in Mouse and Human Hepatoma Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Yiyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"William K.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1016\/S0021-9258(17)33205-2","article-title":"Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol","volume":"251","author":"Poland","year":"1976","journal-title":"J. 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