Liver-type fatty acid binding protein interacts with hepatocyte nuclear factor 4α

FEBS Lett. 2013 Nov 29;587(23):3787-91. doi: 10.1016/j.febslet.2013.09.043. Epub 2013 Oct 15.

Abstract

Hepatocyte nuclear factor 4α (HNF4α) regulates liver type fatty acid binding protein (L-FABP) gene expression. Conversely as shown herein, L-FABP structurally and functionally also interacts with HNF4α. Fluorescence resonance energy transfer (FRET) between Cy3-HNF4α (donor) and Cy5-L-FABP (acceptor) as well as FRET microscopy detected L-FABP in close proximity (~80 Å) to HNF4α, binding with high affinity Kd ~250-300 nM. Circular dichroism (CD) determined that the HNF4α/L-FABP interaction altered protein secondary structure. Finally, L-FABP potentiated transactivation of HNF4α in COS7 cells. Taken together, these data suggest that L-FABP provides a signaling path to HNF4α activation in the nucleus.

Keywords: ACBP; CD; FRET; Fatty acid binding protein; HNF4α; Hepatocyte nuclear factor 4α; L-FABP; LCFA; LCFA-CoA; LSCM; Liver; PPARα; acyl CoA binding protein; circular dichroism; fluorescence resonance energy transfer; hepatocyte nuclear factor 4α; laser scanning confocal microscopy; liver type fatty acid binding protein; long chain fatty acid; long chain fatty acyl CoA; peroxisome proliferator activated receptor-α.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Fatty Acid-Binding Proteins / chemistry
  • Fatty Acid-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 4 / chemistry
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Rats

Substances

  • Fabp1 protein, rat
  • Fatty Acid-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • Hnf4a protein, rat