Modulation of androgen receptor transactivation by FoxH1: A newly identified androgen receptor corepressor

Guangchun Chen, Masatoshi Nomura, Hidetaka Morinaga, Eri Matsubara, Taijiro Okabe, Kiminobu Goto, Toshihiko Yanase, Hong Zheng, Jian Lu, Hajime Nawata

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-β/activin signaling through its interaction with the Smad2-Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2-Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.

Original languageEnglish
Pages (from-to)36355-36363
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number43
DOIs
Publication statusPublished - Oct 28 2005

Fingerprint

Co-Repressor Proteins
Androgen Receptors
Transcriptional Activation
Modulation
Androgens
Prostatic Neoplasms
Dihydrotestosterone
Activins
Transforming Growth Factors
Cell Communication
Proteins
Transcription Factors
Genes
Ligands

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chen, G., Nomura, M., Morinaga, H., Matsubara, E., Okabe, T., Goto, K., ... Nawata, H. (2005). Modulation of androgen receptor transactivation by FoxH1: A newly identified androgen receptor corepressor. Journal of Biological Chemistry, 280(43), 36355-36363. https://doi.org/10.1074/jbc.M506147200

Modulation of androgen receptor transactivation by FoxH1 : A newly identified androgen receptor corepressor. / Chen, Guangchun; Nomura, Masatoshi; Morinaga, Hidetaka; Matsubara, Eri; Okabe, Taijiro; Goto, Kiminobu; Yanase, Toshihiko; Zheng, Hong; Lu, Jian; Nawata, Hajime.

In: Journal of Biological Chemistry, Vol. 280, No. 43, 28.10.2005, p. 36355-36363.

Research output: Contribution to journalArticle

Chen, G, Nomura, M, Morinaga, H, Matsubara, E, Okabe, T, Goto, K, Yanase, T, Zheng, H, Lu, J & Nawata, H 2005, 'Modulation of androgen receptor transactivation by FoxH1: A newly identified androgen receptor corepressor', Journal of Biological Chemistry, vol. 280, no. 43, pp. 36355-36363. https://doi.org/10.1074/jbc.M506147200
Chen, Guangchun ; Nomura, Masatoshi ; Morinaga, Hidetaka ; Matsubara, Eri ; Okabe, Taijiro ; Goto, Kiminobu ; Yanase, Toshihiko ; Zheng, Hong ; Lu, Jian ; Nawata, Hajime. / Modulation of androgen receptor transactivation by FoxH1 : A newly identified androgen receptor corepressor. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 43. pp. 36355-36363.
@article{0210ecc0438f4126a4f49c03d14eaaab,
title = "Modulation of androgen receptor transactivation by FoxH1: A newly identified androgen receptor corepressor",
abstract = "Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-β/activin signaling through its interaction with the Smad2-Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2-Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.",
author = "Guangchun Chen and Masatoshi Nomura and Hidetaka Morinaga and Eri Matsubara and Taijiro Okabe and Kiminobu Goto and Toshihiko Yanase and Hong Zheng and Jian Lu and Hajime Nawata",
year = "2005",
month = "10",
day = "28",
doi = "10.1074/jbc.M506147200",
language = "English",
volume = "280",
pages = "36355--36363",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "43",

}

TY - JOUR

T1 - Modulation of androgen receptor transactivation by FoxH1

T2 - A newly identified androgen receptor corepressor

AU - Chen, Guangchun

AU - Nomura, Masatoshi

AU - Morinaga, Hidetaka

AU - Matsubara, Eri

AU - Okabe, Taijiro

AU - Goto, Kiminobu

AU - Yanase, Toshihiko

AU - Zheng, Hong

AU - Lu, Jian

AU - Nawata, Hajime

PY - 2005/10/28

Y1 - 2005/10/28

N2 - Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-β/activin signaling through its interaction with the Smad2-Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2-Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.

AB - Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-β/activin signaling through its interaction with the Smad2-Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2-Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=27744528468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744528468&partnerID=8YFLogxK

U2 - 10.1074/jbc.M506147200

DO - 10.1074/jbc.M506147200

M3 - Article

C2 - 16120611

AN - SCOPUS:27744528468

VL - 280

SP - 36355

EP - 36363

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 43

ER -