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

Atsushi Yokoyama, Takumi Kouketsu, Yuri Otsubo, Erika Noro, Shun Sawatsubashi, Hiroki Shima, Ikuro Satoh, Sadafumi Kawamura, Takashi Suzuki, Kazuhiko Igarashi, Akira Sugawara

Research output: Contribution to journalArticlepeer-review

Abstract

The androgen receptor (AR) plays an essential role in the development of prostate cancer, and androgen-deprivation therapy is used as a first-line treatment for prostate cancer. However, under androgen-deprivation therapy, castration-resistant prostate cancer inevitably arises, suggesting that the interacting transcriptional coregulators of AR are promising targets for developing novel therapeutics. In this study, we used novel proteomic techniques to evaluate the AR interactome, including biochemically labile binding proteins, which might go undetected by conventional purification methods. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, we identified enhanced at puberty 1 (EAP1) as a novel AR coregulator, whereas its interaction with AR could not be detected under standard biochemical conditions. EAP1 enhanced the transcriptional activity of AR via the E3 ubiquitin ligase activity, and its ubiquitination substrate proteins included AR and HDAC1. Furthermore, in prostate cancer specimens, EAP1 expression was significantly correlated with AR expression as well as a poor prognosis of prostate cancer. Together, these results suggest that EAP1 is a novel AR coregulator that promotes AR activity and potentially plays a role in prostate cancer progression.

Original languageEnglish
Article numberbvab150
JournalJournal of the Endocrine Society
Volume5
Issue number11
DOIs
Publication statusPublished - 2021 Nov 1

Keywords

  • AR
  • EAP1
  • IRF2BPL
  • androgen
  • coactivator
  • nuclear receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'Identification and Functional Characterization of a Novel Androgen Receptor Coregulator, EAP1'. Together they form a unique fingerprint.

Cite this