title: Ligand-independent actions of the orphan receptors/corepressors DAX-1 and SHP in metabolism, reproduction and disease.
abstract: 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 'Orphan Receptors'.
authors.affiliation: Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, S-14183 Huddinge/Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehrlund
authors.forename: Eckardt
authors.initials: E
authors.lastname: Treuter
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D057137:DAX-1 Orphan Nuclear Receptor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012098:Reproduction; D013329:Structure-Activity Relationship
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D002784:Cholesterol