Aryl hydrocarbon receptor repressor

Aryl hydrocarbon receptor repressor (AHRR) is a protein that in humans is encoded by the AHRR gene. It plays a critical role in the regulation of the aryl hydrocarbon receptor (AHR) signaling pathway. This pathway is involved in the mediation of the effects of certain environmental toxins, including dioxins and polycyclic aromatic hydrocarbons, which can bind to the AHR and activate it. The AHRR acts as a feedback inhibitor, helping to regulate and suppress AHR activity, thus playing a key role in maintaining cellular homeostasis and protecting the body from the toxic effects of environmental pollutants.

Function

The AHRR is a member of the bHLH-PAS family of transcription factors, which are involved in sensing environmental and developmental cues. It competes with the aryl hydrocarbon receptor nuclear translocator (ARNT) for binding to AHR, inhibiting the AHR/ARNT complex formation. This inhibition prevents the activation of AHR target genes that are involved in the xenobiotic metabolism, thereby modulating the body's response to harmful compounds. The AHRR itself is induced by the AHR, forming a negative feedback loop that tightly regulates AHR activity.

Gene and Expression

The AHRR gene is located on chromosome 5 in humans. Its expression is tissue-specific and can be induced by exposure to AHR ligands. The regulation of AHRR expression is complex and involves various transcription factors and epigenetic mechanisms, reflecting its role in responding to environmental stimuli.

Clinical Significance

Alterations in the expression or function of the AHRR have been associated with several diseases and conditions. For example, changes in AHRR gene expression have been linked to cancer, particularly in tissues that are exposed to high levels of environmental toxins, such as the lungs and breast. Additionally, AHRR polymorphisms have been studied for their potential association with susceptibility to certain diseases, including various types of cancer and autoimmune diseases.

Research into the AHRR and its pathway offers potential therapeutic targets for diseases caused or exacerbated by dysregulation of the AHR signaling pathway. Modulating AHRR activity could provide a means to mitigate the harmful effects of dioxins and other environmental pollutants, offering a novel approach to disease prevention and treatment.

See Also

• Aryl hydrocarbon receptor
• Transcription factor
• Environmental toxin
• Dioxin
• Polycyclic aromatic hydrocarbon