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Updated: Oct 18, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
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.
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.
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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