Protein kinase A phosphorylates NCoR to enhance its nuclear translocation and repressive function in human prostate cancer cells

J Cell Physiol. 2013 Jun;228(6):1159-65. doi: 10.1002/jcp.24269.

Abstract

Protein kinase A (PKA) phosphorylates diverse protein substrates to modulate their function. In this study, we found that PKA specifically phosphorylates the RD1 (repression domain 1) domain of nuclear receptor corepressor (NCoR). We demonstrated that the Serine-70 of NCoR is identified the critical amino acid for PKA-dependent NCoR phosphorylation. Importantly, we found that PKA-dependent phosphorylation enhances the nuclear translocation of NCoR. More importantly, the activation of PKA enhanced the repressive activity of NCoR in a reporter assay and potentiated the antagonist activity in the androgen receptor (AR)-mediated transcription. Taken together, these results uncover a regulatory mechanism by which PKA positively modulates NCoR function in transcriptional regulation in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Kallikreins / genetics
  • Kallikreins / metabolism
  • Male
  • Mutation
  • Nuclear Receptor Co-Repressor 1 / genetics
  • Nuclear Receptor Co-Repressor 1 / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Serine
  • Signal Transduction
  • Transcription, Genetic
  • Transfection

Substances

  • AR protein, human
  • NCOR1 protein, human
  • Nuclear Receptor Co-Repressor 1
  • Receptors, Androgen
  • Serine
  • Cyclic AMP-Dependent Protein Kinases
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen