title: Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue.
abstract: Nuclear receptors are master regulators of metazoan gene expression with crucial roles during development and in adult physiology. Fushi tarazu factor 1 (FTZ-F1) subfamily members are ancient orphan receptors with homologues from Drosophila to human that regulate diverse gene expression programs important for developmental processes, reproduction and cholesterol homeostasis in an apparently ligand-independent manner. Thus, developmental and tissue-specific cofactors may be particularly important in modulating the transcriptional activities of FTZ-F1 receptors. In Drosophila, the homeodomain protein Fushi tarazu acts as a cofactor for FTZ-F1 (NR5A3), leading to the hypothesis that a similar type of homeodomain cofactor-nuclear receptor relationship might exist in vertebrates. In this study, we have identified and characterized the homeodomain protein Prox1 as a co-repressor for liver receptor homologue 1 (LRH1/NR5A2), a master regulator of cholesterol homeostasis in mammals. Our study suggests that interactions between LRH1 and Prox1 may fulfil roles both during development of the enterohepatic system and in adult physiology of the liver.
authors.affiliation: Department of Biosciences at Novum, Karolinska Institutet, 14157 Huddinge, Sweden.
authors.forename: Knut R
authors.initials: KR
authors.lastname: Steffensen
authors.forename: Elin
authors.initials: E
authors.lastname: Holter
authors.forename: Ann
authors.initials: A
authors.lastname: Båvner
authors.forename: Maria
authors.initials: M
authors.lastname: Nilsson
authors.forename: Markku
authors.initials: M
authors.lastname: Pelto-Huikko
authors.forename: Stanislav
authors.initials: S
authors.lastname: Tomarev
authors.forename: Eckardt
authors.initials: E
authors.lastname: Treuter
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D006655:Histone Deacetylases / Q000032:analysis / Q000378:metabolism; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D054339:Steroidogenic Factor 1; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D000099186:Histone Deacetylase 3
chemical_list: D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D000099186:Histone Deacetylase 3; C082631:NR5A2 protein, human