The region of CQQQKPQRRP of PGC-1alpha interacts with the DNA-binding complex of FXR/RXRalpha

Biochem Biophys Res Commun. 2006 Apr 14;342(3):734-43. doi: 10.1016/j.bbrc.2006.02.015. Epub 2006 Feb 14.

Abstract

PGC-1alpha co-activates transcription by several nuclear receptors. To study the interaction among PGC-1alpha, RXRalpha/FXR, and DNA, we performed electrophoresis mobility shift assays. The RXRalpha/FXR proteins specifically bound to DNA containing the IR-1 sequence in the absence of ligand. When the fusion protein of GST-PGC-1alpha was added to the mixture of RXRalpha/FXR/DNA, the ligand-influenced retardation of the mobility was observed. The ligand for RXRalpha (9-cis-retinoic acid) was necessary for this retardation, whereas, the ligand for FXR, chenodeoxycholic acid, barely had an effect. The results obtained using truncated PGC-1alpha proteins suggested that two regions are necessary for PGC-1alpha to interact with the DNA-binding complex of RXRalpha/FXR. One is the region of the second leucine-rich motif, and the other is that of the amino acid sequence CQQQKPQRRP, present between the second and third leucine-rich motifs. The results obtained with the SPQSS mutation for KPQRR suggested that the basic amino acids are important for the interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding, Competitive
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Retinoid X Receptor alpha / chemistry
  • Retinoid X Receptor alpha / isolation & purification
  • Retinoid X Receptor alpha / metabolism*
  • Transcription Factors / chemistry*
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • PPARGC1A protein, human
  • Peptides
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Retinoid X Receptor alpha
  • Transcription Factors
  • farnesoid X-activated receptor
  • DNA