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.
Written by:
Choi HK, Yoo JY, Jeong MH, Park SY, Shin DM, Jang SW, Yoon HG, Choi KC. Are you the author?
Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, Shinchon-dong, Seodaemun-gu, Seoul, South Korea.
Reference: J Cell Physiol. 2012 Nov 5. Epub ahead of print.
doi: 10.1002/jcp.24269
PubMed Abstract
PMID: 23129261
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