Non-canonical dimerization of the androgen receptor and other nuclear receptors: implications for human disease. Issue 8 (August 2019)

• Record Type: Journal Article
• Authors: Jiménez-Panizo, Alba; Pérez, Paloma; Rojas, Ana M; Fuentes-Prior, Pablo; Estébanez-Perpiñá, Eva
• Is Part Of: Endocrine-related cancer. Volume 26:Issue 8(2019)
• Page Start: R479
• Page End: R497
• Publication Date: 2019-08
• Subjects: androgen receptor -- glucocorticoid receptor -- protein structure -- ligand-binding domain -- multimerization -- prostate cancer -- androgen insensitivity syndromes (AIS) -- hormone resistance; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-19-0132
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : Nuclear receptors are transcription factors that play critical roles in development, homeostasis and metabolism in all multicellular organisms. An important family of nuclear receptors comprises those members that respond to steroid hormones, and which is subdivided in turn into estrogen receptor (ER) isoforms α and β (NR3A1 and A2, respectively), and a second subfamily of so-called oxosteroid receptors. The latter includes the androgen receptor (AR/NR3C4), the glucocorticoid receptor (GR/NR3C1), the mineralocorticoid receptor (MR/NR3C2) and the progesterone receptor (PR/NR3C3). Here we review recent advances in our understanding of the structure-and-function relationship of steroid nuclear receptors and discuss their implications for the etiology of human diseases. We focus in particular on the role played by AR dysregulation in both prostate cancer (PCa) and androgen insensitivity syndromes (AIS), but also discuss conditions linked to mutations of the GR gene as well as those in a non-steroidal receptor, the thyroid hormone receptor (TR). Finally, we explore how these recent results might be exploited for the development of novel and selective therapeutic strategies.