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

Authors
 Hyo‐Kyoung Choi  ;  Jung‐Yoon Yoo  ;  Mi‐Hyeon Jeong  ;  Soo‐Yeon Park  ;  Dong‐Myoung Shin  ;  Sung‐Wuk Jang  ;  Ho‐Geun Yoon  ;  Kyung‐Chul Choi 
Citation
 Journal of Cellular Physiology, Vol.228 : 1159-1165, 2013 
Journal Title
 Journal of Cellular Physiology 
ISSN
 0021-9541 
Issue Date
2013
MeSH
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
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.
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.24269
DOI
10.1002/jcp.24269
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Choi, Hyo Kyoung(최효경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163383
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