title: Nuclear localization of folate receptor alpha: a new role as a transcription factor.
abstract: Folic acid (FA) has traditionally been associated with prevention of neural tube defects; more recent work suggests that it may also be involved in in the prevention of adult onset diseases. As the role of FA in human health and disease expands, it also becomes more critical to understand the mechanisms behind FA action. In this work we examined the hypothesis that folate receptor alpha (FRα) acts as a transcription factor. FRα is a GPI-anchored protein and a component of the caveolae fraction. The work described here shows that FRα translocates to the nucleus, where it binds to cis-regulatory elements at promoter regions of Fgfr4 and Hes1, and regulates their expression. The FRα recognition domain mapped to AT rich regions on the promoters. Until this time FRα has only been considered as a folate transporter, these studies describe a novel role for FRα as a transcription factor.
authors.affiliation: Department of Pediatric Neurosurgery, Ann and Robert H Lurie Children's Hospital of Chicago Research Center and Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA.
authors.forename: Vanda
authors.initials: V
authors.lastname: Boshnjaku
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Shim
authors.forename: Takao
authors.initials: T
authors.lastname: Tsurubuchi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ichi
authors.forename: Elise V
authors.initials: EV
authors.lastname: Szany
authors.forename: Guifa
authors.initials: G
authors.lastname: Xi
authors.forename: Barbara
authors.initials: B
authors.lastname: Mania-Farnell
authors.forename: David G
authors.initials: DG
authors.lastname: McLone
authors.forename: Tadanori
authors.initials: T
authors.lastname: Tomita
authors.forename: C Shekhar
authors.initials: CS
authors.lastname: Mayanil
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D016384:Consensus Sequence; D058975:Folate Receptor 1 / Q000378:metabolism*; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D058975:Folate Receptor 1; D005492:Folic Acid; D051499:Receptor, Fibroblast Growth Factor, Type 4; C496372:Fgfr4 protein, mouse