A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels

Cell Mol Life Sci. 2010 Jun;67(11):1919-27. doi: 10.1007/s00018-010-0302-1. Epub 2010 Feb 26.

Abstract

The androgen receptor protein has specific domains involved in DNA binding, ligand binding, and transactivation, whose activities need to be integrated during transcription activation. The hinge region, more particular a (629)RKLKK(633) motif, seems to play a crucial role in this process. Indeed, although the motif is not part of the DNA-binding domain, its positive residues are involved in optimal DNA binding and nuclear translocation as shown by mutation analysis. When the mutated ARs are forced into the nucleus, however, the residues seem to play different roles in transactivation. Moreover, we show by FRAP analysis that during activation, the AR is distributed in the nucleus in a mobile and two immobile fractions, and that mutations in the (629)RKLKK(633) motif affect the distribution of the AR over these three intranuclear fractions. Taken together, the (629)RKLKK(633) motif is a multifunctional motif that integrates nuclear localization, receptor stability, DNA binding, transactivation potential and intranuclear mobility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • DNA / metabolism
  • Fluorescence Recovery After Photobleaching
  • HeLa Cells
  • Humans
  • Mutagenesis, Site-Directed
  • Protein Stability
  • Protein Structure, Tertiary
  • Receptors, Androgen / chemistry*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Transcriptional Activation

Substances

  • AR protein, human
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • DNA