Ligand-independent actions of the orphan receptors/corepressors DAX-1 and SHP in metabolism, reproduction and disease

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• 作者：Anna Ehrlund ; Eckardt Treuter ; ^{eckardt.treuter@ki.se}
• 关键词：NR0B1 ; DAX-1 ; NR0B2 ; SHP ; Nuclear receptor ; Corepressor
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2012
• 期刊代码：172_09600760
• 类别：med
• 出版时间：July, 2012
• 卷：130
• 期：3-5
• 页码：169-179
• 文件大小：899 K

摘要

DAX-1 and SHP are two closely related atypical orphan members of the nuclear receptor (NR) family that make up the NR0B subfamily. They combine properties of typical NRs and of NR-associated coregulators: both carry the characteristic NR ligand-binding domain but instead of a NR DNA-binding domain they have unique N-terminal regions that contain LxxLL-related NR-binding motifs often found in coregulators. Recent structural data indicate that DAX-1 lacks a ligand-binding pocket and thus should rely on ligand-independent mechanisms of regulation. This might be true, but remains to be proven, for SHP as well. DAX-1 and SHP have in common that they act as transcriptional corepressors of cholesterol metabolism pathways that are related on a molecular level. However, the expression patterns of the two NRs are largely different, with some notable exceptions, and so are the physiological processes they regulate. DAX-1 is mainly involved in steroidogenesis and reproductive development, while SHP plays major roles in maintaining cholesterol and glucose homeostasis. This review highlights the key similarities and differences between DAX-1 and SHP with regard to structure, function and biology and considers what can be learnt from recent research advances in the field.

This article is part of a Special Issue entitled 鈥極rphan Receptors鈥?