Nuclear localization of folate receptor alpha: a new role as a transcription factor

Sci Rep. 2012:2:980. doi: 10.1038/srep00980. Epub 2012 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Consensus Sequence
  • Folate Receptor 1 / metabolism*
  • Folic Acid / pharmacology
  • Humans
  • Mice
  • Promoter Regions, Genetic
  • Protein Binding
  • Receptor, Fibroblast Growth Factor, Type 4 / genetics
  • Receptor, Fibroblast Growth Factor, Type 4 / metabolism
  • Regulatory Elements, Transcriptional
  • Transfection

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Folate Receptor 1
  • Folic Acid
  • Fgfr4 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 4