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The lysine demethylase, KDM4B, is a key molecule in androgen receptor signalling and turnover

Kelly Coffey1, Lynsey Rogerson, Claudia Ryan-Munden

  • 1Solid Tumour Target Discovery Laboratory, Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Nucleic Acids Research
|February 26, 2013
PubMed

Insights

KDM4B enhances prostate cancer progression by regulating androgen receptor (AR) activity and stability. Targeting KDM4B offers a potential therapeutic strategy for prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Androgen receptor (AR) is crucial in prostate cancer (PC) development.
  • Co-regulator proteins modulate AR activity through post-translational modifications.

Purpose of the Study:

  • To identify demethylases involved in AR regulation.
  • To investigate the role of KDM4B in AR function and prostate cancer.

Main Methods:

  • siRNA screening to identify demethylases affecting AR.
  • Assessing KDM4B's enzymatic activity and its effect on AR.
  • Evaluating KDM4B's impact on AR protein stability and ubiquitination.
  • Analyzing KDM4B expression in clinical PC specimens.

Main Results:

  • KDM4B was identified as a key AR co-regulator.
  • KDM4B enhances AR transcriptional activity via demethylation.
  • KDM4B stabilizes AR protein by inhibiting ubiquitination, independent of its enzymatic activity.
  • KDM4B knockdown leads to significant AR protein depletion.
  • KDM4B is an androgen-regulated enzyme.
  • KDM4B expression correlates with advanced prostate cancer grade.

Conclusions:

  • KDM4B and AR have a synergistic relationship, amplifying the androgen response.
  • KDM4B influences AR activity through both demethylation and ubiquitination modulation.
  • KDM4B is a promising therapeutic target for prostate cancer.

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