TR2 and TR4 Orphan Nuclear Receptors: An Overview

Current Topics in Developmental Biology
Shin-Jen LinChawnshang Chang

Abstract

Testicular nuclear receptors 2 and 4 (TR2, TR4), also known as NR2C1 and NR2C2, belong to the nuclear receptor superfamily and were first cloned in 1989 and 1994, respectively. Although classified as orphan receptors, several natural molecules, their metabolites, and synthetic compounds including polyunsaturated fatty acids (PUFAs), PUFA metabolites 13-hydroxyoctadecadienoic acid, 15-hydroxyeicosatetraenoic acid, and the antidiabetic drug thiazolidinediones can transactivate TR4. Importantly, many of these ligands/activators can also transactivate peroxisome proliferator-activated receptor gamma (PPARγ), also known as NR1C3 nuclear receptor. Both TR4 and PPARγ can bind to similar hormone response elements (HREs) located in the promoter of their common downstream target genes. However, these two nuclear receptors, even with shared ligands/activators and shared binding ability for similar HREs, have some distinct functions in many diseases they influence. In cancer, PPARγ inhibits thyroid, lung, colon, and prostate cancers but enhances bladder cancer. In contrast, TR4 inhibits liver and prostate cancer initiation but enhances pituitary corticotroph, liver, and prostate cancer progression. In type 2 diabetes, PPARγ increases insul...Continue Reading

Citations

Jan 16, 2018·Nuclear Receptor Research·Shari BodofskyBruce Wightman
Feb 28, 2019·Molecular Genetics & Genomic Medicine·Jessada ThutkawkorapinEmma Tham
Mar 7, 2019·Diabetes/metabolism Research and Reviews·Zhe-Zhen LiaoXin-Hua Xiao
Jun 20, 2019·Cells·Masaki ShiotaMasatoshi Eto
Jul 6, 2020·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Moriah P BellissimoJessica A Alvarez
Dec 9, 2020·Molecular Aspects of Medicine·Camilla H K Hughes, Bruce D Murphy
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Gloria BarbaraniAntonella E Ronchi
Oct 8, 2021·Frontiers in Molecular Biosciences·Huan WangHaiyang Wu

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