AhR promotes phosphorylation of ARNT isoform 1 in human T cell malignancies as a switch for optimal AhR activity-Reference-Cited by-同舟云学术

AhR promotes phosphorylation of ARNT isoform 1 in human T cell malignancies as a switch for optimal AhR activity

Published:2022-03-15 Issue:12 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Bourner Luke A.¹²^ORCID,Muro Israel¹^ORCID,Cooper Amy M.¹²^ORCID,Choudhury Barun K.¹,Bailey Aaron O.³^ORCID,Russell William K.³^ORCID,Khanipov Kamil¹^ORCID,Golovko George¹^ORCID,Wright Casey W.¹²⁴^ORCID

Affiliation:

1. Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555

2. Toxicology Training Program, The University of Texas Medical Branch at Galveston, Galveston, TX 77555

3. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555

4. Sealy Center for Environmental Health, The University of Texas Medical Branch at Galveston, Galveston, TX 77555

Abstract

Significance Nontoxic agonists and antagonists of the aryl hydrocarbon receptor (AhR) hold high therapeutic potential for treating autoimmune disease and cancer. However, AhR activation by different ligands can lead to opposing phenotypical outcomes in a cell- and tissue-specific manner. In this study, we demonstrate that proportional flux in the levels of aryl hydrocarbon receptor nuclear translocator (ARNT) isoforms 1 and 3 modulates AhR signaling in terms of amplitude and expression of distinct gene programs. These results delineate a molecular mechanism of ARNT isoform–mediated AhR regulation, simplify our understanding of a complex AhR signaling pathway, and provide feasibility for ARNT-targeted therapies that could be used in conjunction with nontoxic AhR ligands for the purpose of immunomodulation.

Funder

HHS | NIH | National Institute of Environmental Health Sciences

Cancer Prevention and Research Institute of Texas

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2114336119

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