The nomenclature of hepatocyte nuclear factor-4 receptors is agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [1-2]. While linoleic acid has been identified as the endogenous ligand for HNF4α its function remains ambiguous [5]. HNF4γ has yet to be paired with an endogenous ligand.

* Key recommended reading is highlighted with an asterisk

Babeu JP, Boudreau F. (2014) Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks. World J Gastroenterol, 20 (1): 22-30. [PMID:24415854]

* Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev, 58 (4): 798-836. [PMID:17132856]

* Garattini E, Bolis M, Gianni' M, Paroni G, Fratelli M, Terao M. (2016) Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer. Oncotarget, 7 (27): 42661-42682. [PMID:26894976]

Gerbal-Chaloin S, Iankova I, Maurel P, Daujat-Chavanieu M. (2013) Nuclear receptors in the cross-talk of drug metabolism and inflammation. Drug Metab Rev, 45 (1): 122-44. [PMID:23330545]

* Germain P, Staels B, Dacquet C, Spedding M, Laudet V. (2006) Overview of nomenclature of nuclear receptors. Pharmacol Rev, 58 (4): 685-704. [PMID:17132848]

Huang P, Chandra V, Rastinejad F. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu Rev Physiol, 72: 247-72. [PMID:20148675]

Hwang-Verslues WW, Sladek FM. (2010) HNF4α--role in drug metabolism and potential drug target?. Curr Opin Pharmacol, 10 (6): 698-705. [PMID:20833107]

* Lu H. (2016) Crosstalk of HNF4α with extracellular and intracellular signaling pathways in the regulation of hepatic metabolism of drugs and lipids. Acta Pharm Sin B, 6 (5): 393-408. [PMID:27709008]

Sladek FM. (2011) What are nuclear receptor ligands?. Mol Cell Endocrinol, 334 (1-2): 3-13. [PMID:20615454]

* Walesky C, Apte U. (2015) Role of hepatocyte nuclear factor 4α (HNF4α) in cell proliferation and cancer. Gene Expr, 16 (3): 101-8. [PMID:25700366]

1. Alexander SPH, Cidlowski JA, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors. Br J Pharmacol, 176 Suppl 1: S229-S246. [PMID:31710718]

2. Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev, 58 (4): 798-836. [PMID:17132856]

3. Jiang G, Nepomuceno L, Hopkins K, Sladek FM. (1995) Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors. Mol Cell Biol, 15 (9): 5131-43. [PMID:7651430]

4. Kiselyuk A, Lee SH, Farber-Katz S, Zhang M, Athavankar S, Cohen T, Pinkerton AB, Ye M, Bushway P, Richardson AD et al.. (2012) HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter. Chem Biol, 19 (7): 806-18. [PMID:22840769]

5. Yuan X, Ta TC, Lin M, Evans JR, Dong Y, Bolotin E, Sherman MA, Forman BM, Sladek FM. (2009) Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS ONE, 4 (5): e5609. [PMID:19440305]

Frances M. Sladek, Ph.D. Professor of Cell Biology and Toxicologist Associate Director, UCR Stem Cell Center Department of Cell Biology and Neuroscience 2115 Biological Sciences Building University of California Riverside, CA 92521-0314