title: Steroidogenic factor-1 is a sphingolipid binding protein.
abstract: Steroidogenic factor (SF1, NR5A1, Ad4BP) is an orphan nuclear receptor that is essential for steroid hormone-biosynthesis and endocrine development. Studies have found that the ability of this receptor to increase target gene expression can be regulated by post-translational modification, subnuclear localization, and protein-protein interactions. Recent crystallographic studies and our mass spectrometric analyses of the endogenous receptor have demonstrated an integral role for ligand-binding in the control of SF1 transactivation activity. Herein, we discuss our findings that sphingosine is an endogenous ligand for SF1. These studies and the structural findings of others have demonstrated that the receptor can bind both sphingolipids and phospholipids. Thus, it is likely that multiple bioactive lipids are ligands for SF1 and that these lipids will differentially act to control SF1 activity in a context-dependent manner. Finally, these findings highlight a central role for bioactive lipids as mediators of trophic hormone-stimulated steroid hormone biosynthesis.
authors.affiliation: School of Biology and the Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332-0230, United States.
authors.forename: Aarti N
authors.initials: AN
authors.lastname: Urs
authors.forename: Eric
authors.initials: E
authors.lastname: Dammer
authors.forename: Samuel
authors.initials: S
authors.lastname: Kelly
authors.forename: Elaine
authors.initials: E
authors.lastname: Wang
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Merrill
authors.forename: Marion B
authors.initials: MB
authors.lastname: Sewer
mesh_terms: D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000378:metabolism; D054339:Steroidogenic Factor 1; D013256:Steroids / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D013107:Sphingolipids; D054339:Steroidogenic Factor 1; D013256:Steroids; D014157:Transcription Factors; D013110:Sphingosine