Nuclear Receptors and Disease


Nuclear receptors are ligand‐modulated transcription factors that act in the nucleus to regulate target gene transcription through interaction with cofactor proteins. Owing to their roles in many diverse cellular processes, nuclear receptors are important therapeutic targets and aberrant receptor action results in significant human disease.

Keywords: transcription factors; corepressor; ligand; coactivator; repression

Figure 1.

Model of a full‐length homodimeric estrogen receptor. The extreme C‐terminal domain is represented as a gold sphere. Helix 12 is shown in yellow. The ligand is shown as space‐filling pink spheres in the LBD. The flexible hinge domain is modeled as a pink ribbon. Zinc ions are represented as silver spheres. The extreme N‐terminal domain (A/B) is shown as a red sphere. The LBD structure is from Protein Data Bank (PDB) entry 1ERE; the DBD structure is from PDB entry 1HCQ.

Figure 2.

The action of ligand on a PPARγ ligand‐binding domain. In the absence of activating ligand (or with antagonist present, as shown here) helix 12 (yellow) is disordered and the corepressor (blue) binds to the surface of the receptor (left). In the presence of activating ligand (middle), helix 12 adopts an active conformation and coactivator (red) is recruited to the receptor (right). The corepressor structure is from PDB entry 1KKQ; the ligand and coactivator structures are from PDB entry 2PRG.



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Further Reading

Collingwood TN, Urnov FD and Wolffe AP (1999) Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription. Journal of Molecular Endocrinology 23: 255–275.

Hu X and Lazar MA (2000) Transcriptional repression by nuclear hormone receptors. Trends in Endocrinology and Metabolism 11: 6–10.

Leo C and Chen JD (2000) The SRC family of nuclear receptor coactivators. Gene 245: 1–11.

Melnick A and Licht JD (1999) Deconstructing a disease: RARα, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 93: 3167–3215.

Shang Y, Hu X, DiRenzo J, Lazar MA and Brown M (2000) Cofactor dynamics and sufficiency in estrogen receptor‐regulated transcription. Cell 103: 843–852.

Web Links

Nuclear receptor subfamily 4, group A, member 2 (NR4A2); LocusID: 4929. LocusLink:

Peroxisome proliferative activated receptor, gamma (PPARG); LocusID: 5468. LocusLink:

Promyelocytic leukemia (PML); LocusID: 5371. LocusLink:

Thyroid hormone receptor, beta (THRB); LocusID: 7068. LocusLink:

Zinc‐finger protein 145 (ZNF145); LocusID: 7704. LocusLink:

Nuclear receptor subfamily 4, group A, member 2 (NR4A2); MIM number: 601828. OMIM:‐post/Omim/dispmim?601828

Peroxisome proliferative activated receptor, gamma (PPARG); MIM number: 601487. OMIM:‐post/Omim/dispmim?601487

Promyelocytic leukemia (PML); MIM number: 102578. OMIM:‐post/Omim/dispmim?102578

Thyroid hormone receptor, beta (THRB); MIM number: 190160. OMIM:‐post/Omim/dispmim?190160

Zinc‐finger protein 145 (ZNF145); MIM number: 176797. OMIM:‐post/Omim/dispmim?176797

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How to Cite close
Love, James Daniel(Jan 2006) Nuclear Receptors and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0006024]