Nuclear Receptor Regulation in Cellular Processes

Nuclear receptors constitute a superfamily of transcription factors that translate hormonal, metabolic and environmental signals into precise gene‐expression programmes. Each receptor comprises a conserved DNA‐binding domain and a ligand‐binding domain that together recruit coactivators or corepressors to control transcription. While classical receptors respond to steroids, thyroid hormones or vitamins, orphan nuclear receptors bind no known endogenous ligand yet exert pivotal regulatory roles. Through genomic and non‐genomic pathways, nuclear receptors govern cell proliferation, differentiation, apoptosis, metabolism and inflammatory responses. They integrate post-translational modifications such as phosphorylation, ubiquitination and acetylation to fine-tune receptor stability, subcellular localisation and transcriptional activity. Crosstalk with signalling networks—most notably kinase cascades and the NF-κB system—extends their influence on immune homeostasis and stress responses. Dysregulation of receptor expression or cofactor recruitment underlies a range of diseases from cancer and metabolic syndrome to cardiovascular and neurodegenerative disorders. Harnessing receptor function through synthetic ligands, peptides or gene-editing tools offers routes to novel therapeutics and precision medicine.

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Nuclear Receptor Regulation in Cellular Processes publication trend

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Technical terms

Orphan nuclear receptor: A transcription factor lacking an identified endogenous ligand but regulating gene expression.

Ligand-binding domain: A receptor region that recognises small-molecule ligands or mediates protein–protein interactions.

Coactivator: A protein that binds activated receptors to enhance transcription of target genes.

Ubiquitination: A post-translational modification tagging proteins for degradation or functional modulation.

Autophagic flux: The dynamic process of autophagosome formation and cargo degradation in lysosomes.

NF-κB: A family of transcription factors central to inflammatory and immune responses.

References

1. In Silico Discovery of Stapled Peptide Inhibitor Targeting the Nur77‐PPARγ Interaction and Its Anti‐Breast‐Cancer Efficacy. Advanced Science (2024).
2. Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues. Cells (2019).
3. Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis. Biomolecules (2015).