What is it about?
We demonstrate that proportional flux in the levels of aryl hydrocarbon receptor nuclear translocator (ARNT, the binding partner of AhR) isoforms 1 and 3 modulates AhR signaling in terms of amplitude and expression of distinct gene programs. Molecular studies identified the unique casein kinase 2 (CK2) phosphorylation site within isoform 1 as an essential parameter to the mechanism of ARNT isoform–specific regulation of AhR signaling.
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Why is it important?
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 therapeutic intervention in hematological diseases via immunomodulation.
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This page is a summary of: AhR promotes phosphorylation of ARNT isoform 1 in human T cell malignancies as a switch for optimal AhR activity, Proceedings of the National Academy of Sciences, March 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2114336119.
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