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

Hyo-Kyoung Choi1, Jung-Yoon Yoo, Mi-Hyeon Jeong

  • 1Department 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

Journal of Cellular Physiology
|November 7, 2012
PubMed

Insights

Protein kinase A (PKA) enhances nuclear receptor corepressor (NCoR) function by phosphorylating its repression domain. This PKA-mediated phosphorylation increases NCoR

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Cancer Research

Background:

  • Protein kinase A (PKA) is a key enzyme regulating diverse cellular processes through protein phosphorylation.
  • Nuclear receptor corepressor (NCoR) plays a crucial role in gene transcription repression.
  • Dysregulation of transcriptional regulation is implicated in various diseases, including prostate cancer.

Purpose of the Study:

  • To investigate the specific interaction between PKA and NCoR.
  • To elucidate the functional consequences of PKA-mediated NCoR phosphorylation.
  • To understand the role of this regulatory mechanism in prostate cancer.

Main Methods:

  • Phosphorylation assays to identify PKA substrates.
  • Site-directed mutagenesis to pinpoint critical phosphorylation sites.
  • Reporter assays and Western blotting to assess NCoR nuclear translocation and transcriptional activity.

Main Results:

  • PKA specifically phosphorylates the repression domain 1 (RD1) of NCoR.
  • Serine-70 on NCoR is identified as the critical residue for PKA-dependent phosphorylation.
  • PKA activation enhances NCoR nuclear translocation, repressive activity, and androgen receptor (AR)-mediated transcription antagonism.

Conclusions:

  • PKA positively modulates NCoR function through phosphorylation of Serine-70.
  • This regulatory pathway enhances NCoR's role in transcriptional repression.
  • The PKA-NCoR axis represents a potential therapeutic target in prostate cancer.

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