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Protein Kinase A phosphorylates NCoR to enhance its nuclear translocation and repressive function in human prostate cancer cells
Author(s) -
Choi HyoKyoung,
Yoo JungYoon,
Jeong MiHyeon,
Park SooYeon,
Shin DongMyoung,
Jang SungWuk,
Yoon HoGeun,
Choi KyungChul
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24269
Subject(s) - corepressor , nuclear receptor , phosphorylation , nuclear export signal , microbiology and biotechnology , cancer research , transcription factor , nuclear receptor co repressor 1 , protein kinase a , chemistry , biology , biochemistry , cell nucleus , gene , nucleus
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. J. Cell. Physiol. 228: 1159–1165, 2013. © 2012 Wiley Periodicals, Inc.