title: Liver-type fatty acid binding protein interacts with hepatocyte nuclear factor 4α.
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.
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843-4466, United States.
authors.forename: Avery L
authors.initials: AL
authors.lastname: McIntosh
authors.forename: Anca D
authors.initials: AD
authors.lastname: Petrescu
authors.forename: Heather A
authors.initials: HA
authors.lastname: Hostetler
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D051557:Hepatocyte Nuclear Factor 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051381:Rats
chemical_list: C493321:Fabp1 protein, rat; D050556:Fatty Acid-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C496594:Hnf4a protein, rat
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