The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway

J Biol Chem. 2003 Nov 14;278(46):46087-93. doi: 10.1074/jbc.M306219200. Epub 2003 Sep 4.


The androgen receptor (AR), a member of the nuclear hormone receptor superfamily, functions as a ligand-dependent transcription factor that regulates genes involved in cell proliferation and differentiation. Using a C-terminal region of the human AR in a yeast two-hybrid screen, we have identified RACK1 (receptor for activated C kinase-1) as an AR-interacting protein. In this report we found that RACK1, which was previously shown to be a protein kinase C (PKC)-anchoring protein that determines the localization of activated PKCbetaII isoform, facilitates ligand-independent AR nuclear translocation upon PKC activation by indolactam V. We also observed RACK1 to suppress ligand-dependent and -independent AR transactivation through PKC activation. In chromatin immunoprecipitation assays, we demonstrate a decrease in AR recruitment to the AR-responsive prostate-specific antigen (PSA) promoter following stimulation of PKC. Furthermore, prolonged exposure to indolactam V, a PKC activator, caused a reduction in PSA mRNA expression in prostate cancer LNCaP cells. Finally, we found PKC activation to have a repressive effect on AR and PSA protein expression in androgen-treated LNCaP cells. Our data suggest that RACK1 may function as a scaffold for the association and modification of AR by PKC enabling translocation of AR to the nucleus but rendering AR unable to activate transcription of its target genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Blotting, Western
  • COS Cells
  • Cell Differentiation
  • Cell Division
  • Cell Line, Tumor
  • Chromatin / metabolism
  • Gene Deletion
  • Humans
  • Indoles / pharmacology
  • Lactams / pharmacology
  • Ligands
  • Microscopy, Fluorescence
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Receptors for Activated C Kinase
  • Receptors, Androgen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Two-Hybrid System Techniques
  • beta-Galactosidase / metabolism


  • Chromatin
  • Indoles
  • Lactams
  • Ligands
  • Peptides
  • Protein Isoforms
  • RNA, Messenger
  • Receptors for Activated C Kinase
  • Receptors, Androgen
  • peptide I
  • indolactam V
  • Protein Kinase C
  • beta-Galactosidase