How do adopted orphan receptors regulate gene expression?

Adopted orphan receptors are a type of nuclear receptor that do not have a known endogenous ligand. Instead, they can be activated by synthetic ligands or by binding to other proteins. These receptors play a crucial role in regulating gene expression by binding to specific DNA sequences called response elements in the promoter regions of target genes.

When a ligand binds to an adopted orphan receptor, it causes a conformational change in the receptor that allows it to interact with coactivator proteins. These coactivators help recruit other proteins, such as histone acetyltransferases and chromatin remodeling complexes, to the promoter region of target genes. This leads to the activation of gene transcription and the production of mRNA.

On the other hand, when the ligand dissociates from the receptor, corepressor proteins are recruited instead. These corepressors help recruit histone deacetylases and other proteins that promote chromatin condensation, leading to gene repression.

Overall, adopted orphan receptors play a critical role in regulating gene expression by acting as transcription factors that can either activate or repress the transcription of target genes in response to ligand binding.

Adopted Orphan Receptors: Regulating Gene Expression

Adopted orphan receptors (AORs) are nuclear hormone receptors that lack known endogenous ligands but can regulate gene expression in response to specific stimuli. They play a crucial role in various physiological processes and diseases.

Mechanism of Action:

When an AOR binds to its specific stimulus, it undergoes conformational changes that expose its ligand-binding domain (LBD). This allows coactivators or corepressors to interact with the LBD, leading to either activation or repression of target gene expression.

Regulation of Gene Expression:

AORs can regulate gene expression through several mechanisms:

- Direct DNA Binding: AORs can bind to specific DNA sequences called response elements (REs) in the promoters of target genes, either activating or repressing transcription.
- Tethering of Transcription Factors: AORs can interact with other transcription factors or coactivators, tethering them to the regulatory regions of target genes and facilitating gene activation.
- Chromatin Remodeling: AORs can recruit chromatin-modifying enzymes to target gene promoters, altering chromatin structure and making the DNA more accessible for transcription initiation.

Stimuli and Biological Roles:

AORs respond to a variety of stimuli, including:

- Hormones: AORs such as the peroxisome proliferator-activated receptor (PPAR) are regulated by fatty acid ligands.
- Xenobiotics: The aryl hydrocarbon receptor (AhR) is activated by environmental pollutants like dioxins.
- Cytokines: The nuclear factor kappa B (NF-κB) family of AORs is activated by inflammatory cytokines.

Biological roles of AORs include:

- Metabolism: AORs like PPARs regulate lipid and glucose metabolism.
- Immune Response: AORs like NF-κB control inflammation and immune cell function.
- Toxicology: AORs like AhR protect cells from environmental toxins.
- Cancer: AORs can act as tumor suppressors or oncogenes in different cancers.

Conclusion:

Adopted orphan receptors are key regulators of gene expression in response to diverse stimuli. They play essential roles in various physiological processes and diseases. Understanding the mechanisms and regulation of AORs provides valuable insights for therapeutic interventions.