Identification and Functional Characterization of a Novel Androgen Receptor Coregulator, EAP1

Atsushi Yokoyama1, Takumi Kouketsu1, Yuri Otsubo1

  • 1Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan.

Insights

Researchers discovered Enhanced at Puberty 1 (EAP1) as a novel androgen receptor (AR) coregulator. EAP1 promotes AR activity and is linked to prostate cancer progression, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Androgen receptor (AR) is crucial in prostate cancer development.
  • Androgen-deprivation therapy resistance leads to castration-resistant prostate cancer.
  • AR-interacting transcriptional coregulators are potential therapeutic targets.

Purpose of the Study:

  • To identify novel AR coregulators using advanced proteomic techniques.
  • To investigate the role of Enhanced at Puberty 1 (EAP1) in AR activity and prostate cancer.

Main Methods:

  • Utilized rapid immunoprecipitation mass spectrometry of endogenous proteins.
  • Evaluated the AR interactome, including biochemically labile binding proteins.
  • Assessed EAP1's effect on AR transcriptional activity and ubiquitination substrates.

Main Results:

  • Identified EAP1 as a novel AR coregulator, undetectable by standard methods.
  • EAP1 enhances AR transcriptional activity through its E3 ubiquitin ligase activity.
  • AR and HDAC1 were identified as EAP1 ubiquitination substrates.
  • EAP1 expression correlates with AR expression and poor prognosis in prostate cancer specimens.

Conclusions:

  • EAP1 is a novel AR coregulator that promotes AR activity.
  • EAP1 may play a significant role in prostate cancer progression.
  • EAP1 represents a promising therapeutic target for prostate cancer.

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