title: Protein kinase A phosphorylates NCoR to enhance its nuclear translocation and repressive function in human prostate cancer cells.
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.
authors.affiliation: 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. choikc75@amc.seoul.kr
authors.forename: Hyo-Kyoung
authors.initials: HK
authors.lastname: Choi
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.forename: Mi-Hyeon
authors.initials: MH
authors.lastname: Jeong
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Dong-Myoung
authors.initials: DM
authors.lastname: Shin
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
mesh_terms: D021581:Active Transport, Cell Nucleus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C410798:AR protein, human; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D011944:Receptors, Androgen; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen