Aryl hydrocarbon receptors (AhRs) are a class of ligand-activated transcription factors found in many organisms, including humans. They belong to the basic helix-loop-helix/Per-ARNT-Sim (bHLH/PAS) protein family and play a crucial role in modulating gene expression in response to environmental stimuli.
AhRs are primarily known for their involvement in the metabolism of xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which are common pollutants found in industrial processes and cigarette smoke. Upon binding to a ligand, AhRs translocate to the nucleus and form heterodimers with the aryl hydrocarbon receptor nuclear translocator (ARNT), allowing them to bind to specific sequences in the DNA known as xenobiotic response elements (XREs). This binding activates the transcription of target genes involved in xenobiotic metabolism, detoxification, and cellular defense mechanisms.
Apart from their role in xenobiotic metabolism, AhRs also play a critical role in various physiological processes, including immune modulation, cell cycle regulation, development, and differentiation. Dysregulation of AhR signaling has been implicated in several diseases, including cancer, autoimmune disorders, neurodevelopmental disorders, and metabolic disorders.
Due to the diverse functions of AhRs and their involvement in various diseases, they are an area of active research. Understanding the molecular mechanisms governing AhR activation and identifying their downstream targets may provide valuable insights for therapeutic interventions and environmental risk assessments.
