Abstract
The basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH-PAS) domain family of transcription factors mediates cellular responses to a variety of internal and external stimuli. As functional transcription factors, these proteins act as bHLH-PAS heterodimers and can be further sub-classified into sensory/activated subunits and regulatory or ARNT-like proteins. This class of proteins act as master regulators of the bHLHPAS superfamily of transcription factors that mediate circadian rhythm gene programs, innate and adaptive immune responses, oxygen-sensing mechanisms and compensate for deleterious environmental exposures. Some contribute to the etiology of human pathologies including cancer because of their effects on cell growth and metabolism. We will review the canonical roles of ARNT and ARNT-like proteins with an emphasis on coactivator selectivity and recruitment. We will also discuss recent advances in our understanding of noncanonical DNA-binding independent or off-target roles of ARNT that are uncoupled from its classic heterodimeric bHLH-PAS binding partners. Understanding the DNA binding-independent functions of ARNT may identify novel therapeutic options for the treatment of a large spectrum of disease states.
Keywords: ARNT, bHLH-PAS, circadian rhythm, cross-talk, environmental sensor, oxygen sensing, transcription factor.
Current Molecular Medicine
Title:The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Family of Proteins: Transcriptional Modifiers with Multi-Functional Protein Interfaces
Volume: 13 Issue: 7
Author(s): M. P. Labrecque, G. G. Prefontaine and T. V. Beischlag
Affiliation:
Keywords: ARNT, bHLH-PAS, circadian rhythm, cross-talk, environmental sensor, oxygen sensing, transcription factor.
Abstract: The basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH-PAS) domain family of transcription factors mediates cellular responses to a variety of internal and external stimuli. As functional transcription factors, these proteins act as bHLH-PAS heterodimers and can be further sub-classified into sensory/activated subunits and regulatory or ARNT-like proteins. This class of proteins act as master regulators of the bHLHPAS superfamily of transcription factors that mediate circadian rhythm gene programs, innate and adaptive immune responses, oxygen-sensing mechanisms and compensate for deleterious environmental exposures. Some contribute to the etiology of human pathologies including cancer because of their effects on cell growth and metabolism. We will review the canonical roles of ARNT and ARNT-like proteins with an emphasis on coactivator selectivity and recruitment. We will also discuss recent advances in our understanding of noncanonical DNA-binding independent or off-target roles of ARNT that are uncoupled from its classic heterodimeric bHLH-PAS binding partners. Understanding the DNA binding-independent functions of ARNT may identify novel therapeutic options for the treatment of a large spectrum of disease states.
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Labrecque P. M., Prefontaine G. G. and Beischlag V. T., The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Family of Proteins: Transcriptional Modifiers with Multi-Functional Protein Interfaces, Current Molecular Medicine 2013; 13 (7) . https://dx.doi.org/10.2174/15665240113139990042
DOI https://dx.doi.org/10.2174/15665240113139990042 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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