AHR - Aryl hydrocarbon receptor (repressor) | Elisa - Clia - Antibody - Protein

Background:

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in various physiological processes, including xenobiotic metabolism, immune regulation, and cellular differentiation. AHR is activated by a diverse range of ligands, including environmental pollutants such as dioxins, polycyclic aromatic hydrocarbons (PAHs), and certain dietary compounds. Upon ligand binding, AHR translocates to the nucleus and forms a complex with other proteins, regulating the expression of target genes involved in detoxification, inflammation, and cellular proliferation. Dysregulation of AHR signaling has been implicated in numerous diseases, including cancer, immune disorders, and metabolic syndromes. Understanding the molecular mechanisms underlying AHR activation and signaling pathways provides insights into its roles in health and disease, offering potential targets for therapeutic intervention. Ongoing research continues to unravel the complexities of AHR biology and its implications for human health.

Protein Structure:

• Molecular Weight: Approximately 96 kDa.
• Primary Structure: AHR is composed of 848 amino acids.
• Domains:
• bHLH (basic Helix-Loop-Helix): Involved in DNA binding and dimerization.
• PAS (Per-ARNT-SIM): Mediates interactions with other proteins and ligands.
• TAD (Transactivation Domain): Located in the C-terminal region, involved in the activation of transcription.
• Subcellular Localization: In the absence of a ligand, AHR resides in the cytoplasm. Upon ligand binding, it translocates to the nucleus.

Classification and Subtypes:

• Protein Family: AHR belongs to the bHLH-PAS family of transcription factors.
• Subtypes: No distinct subtypes of AHR are identified, but it can form heterodimers with other proteins like ARNT (AHR Nuclear Translocator) to function.

Function and Biological Significance:

• Xenobiotic Metabolism: AHR regulates the expression of enzymes involved in the metabolism of xenobiotics, including cytochrome P450 enzymes like CYP1A1 and CYP1B1.
• Development: It is involved in the regulation of developmental processes, including vascular development and the differentiation of various cell types.
• Immune Response: AHR influences the immune system, modulating the differentiation and function of T cells and other immune cells.
• Circadian Rhythm: AHR has been implicated in the regulation of circadian rhythms through interactions with circadian clock genes.
• Tumorigenesis: AHR plays a dual role in cancer, acting as either a tumor promoter or suppressor depending on the context and type of cancer.

Interactions:

• ARNT: AHR forms a heterodimer with ARNT, which is essential for its DNA-binding and transcriptional activity.
• HSP90 (Heat Shock Protein 90): In the cytoplasm, AHR is part of a complex with HSP90, which stabilizes it and prevents its degradation.
• Coactivators and Corepressors: AHR interacts with various coactivators and corepressors to modulate the transcription of target genes.

Clinical Issues:

• Toxicology: AHR mediates the toxic effects of dioxins and related environmental pollutants, leading to toxic responses like chloracne, immune suppression, and carcinogenesis.
• Autoimmunity and Inflammation: Dysregulation of AHR signaling is implicated in autoimmune diseases and chronic inflammatory conditions.
• Cancer: Altered AHR signaling is associated with various cancers, including liver, lung, and breast cancers. It can influence cancer cell proliferation, apoptosis, and metastasis.
• Developmental Disorders: Abnormal AHR activation during development can lead to teratogenic effects and developmental abnormalities.

Summary:

The Aryl Hydrocarbon Receptor (AHR) is a pivotal transcription factor in the regulation of xenobiotic metabolism, developmental processes, and immune responses. It operates by forming a complex with ARNT and other proteins to modulate gene expression. AHR's role in mediating the effects of environmental toxins has significant implications for toxicology, cancer, and immune regulation. Understanding the diverse functions and interactions of AHR is crucial for developing therapeutic strategies to mitigate its adverse effects in various diseases.