p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation

Maofu Fu, Chenguang Wang, Anne T. Reutens, Jian Wang, Ruth H. Angeletti, Linda Siconolfi-Baez, Vasily Ogryzko, Maria Laura Avantaggiati, Richard G. Pestell

Research output: Contribution to journalArticle

286 Citations (Scopus)

Abstract

The androgen receptor (AR) is a sequence-specific DNA-binding protein that plays a key role in prostate cancer cellular proliferation by dihydrotestosterone and the induction of secondary sexual characteristics. In this study we demonstrate that the AR can be modified by acetylation in vitro and in vivo. p300 and p300/cAMP-response element-binding protein acetylated the AR at a highly conserved lysine-rich motif carboxyl-terminal to the zinc finger DNA-binding domain. [14C]acetate-labeling experiments demonstrated that AR acetylation by p300 in cultured cells requires the same residues identified in vitro. Point mutation of the AR acetylation site (K632A/K633A) abrogated dihydrotestosterone-dependent transactivation of the AR in cultured cells. Mutation of the p300 CH3 region or the p300/cAMP-response element- binding protein histone acetylase domain reduced ligand-dependent AR function. The identification of the AR as a direct target of histone acetyltransferase co-activators has important implications for targeting inhibitors of AR function.

Original languageEnglish (US)
Pages (from-to)20853-20860
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number27
DOIs
StatePublished - Jul 7 2000

Fingerprint

Cyclic AMP Response Element-Binding Protein
Androgen Receptors
Transcriptional Activation
Hormones
Acetylation
Histone Acetyltransferases
Dihydrotestosterone
Cultured Cells
Cells
Zinc Fingers
DNA-Binding Proteins
Point Mutation
Labeling
Lysine
Zinc
Prostatic Neoplasms
Acetates
Cell Proliferation
Ligands
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. / Fu, Maofu; Wang, Chenguang; Reutens, Anne T.; Wang, Jian; Angeletti, Ruth H.; Siconolfi-Baez, Linda; Ogryzko, Vasily; Avantaggiati, Maria Laura; Pestell, Richard G.

In: Journal of Biological Chemistry, Vol. 275, No. 27, 07.07.2000, p. 20853-20860.

Research output: Contribution to journalArticle

Fu, M, Wang, C, Reutens, AT, Wang, J, Angeletti, RH, Siconolfi-Baez, L, Ogryzko, V, Avantaggiati, ML & Pestell, RG 2000, 'p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation', Journal of Biological Chemistry, vol. 275, no. 27, pp. 20853-20860. https://doi.org/10.1074/jbc.M000660200
Fu, Maofu ; Wang, Chenguang ; Reutens, Anne T. ; Wang, Jian ; Angeletti, Ruth H. ; Siconolfi-Baez, Linda ; Ogryzko, Vasily ; Avantaggiati, Maria Laura ; Pestell, Richard G. / p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 27. pp. 20853-20860.
@article{3cb6dc2fbb7144fcb9d41b79339fdbc7,
title = "p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation",
abstract = "The androgen receptor (AR) is a sequence-specific DNA-binding protein that plays a key role in prostate cancer cellular proliferation by dihydrotestosterone and the induction of secondary sexual characteristics. In this study we demonstrate that the AR can be modified by acetylation in vitro and in vivo. p300 and p300/cAMP-response element-binding protein acetylated the AR at a highly conserved lysine-rich motif carboxyl-terminal to the zinc finger DNA-binding domain. [14C]acetate-labeling experiments demonstrated that AR acetylation by p300 in cultured cells requires the same residues identified in vitro. Point mutation of the AR acetylation site (K632A/K633A) abrogated dihydrotestosterone-dependent transactivation of the AR in cultured cells. Mutation of the p300 CH3 region or the p300/cAMP-response element- binding protein histone acetylase domain reduced ligand-dependent AR function. The identification of the AR as a direct target of histone acetyltransferase co-activators has important implications for targeting inhibitors of AR function.",
author = "Maofu Fu and Chenguang Wang and Reutens, {Anne T.} and Jian Wang and Angeletti, {Ruth H.} and Linda Siconolfi-Baez and Vasily Ogryzko and Avantaggiati, {Maria Laura} and Pestell, {Richard G.}",
year = "2000",
month = "7",
day = "7",
doi = "10.1074/jbc.M000660200",
language = "English (US)",
volume = "275",
pages = "20853--20860",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "27",

}

TY - JOUR

T1 - p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation

AU - Fu, Maofu

AU - Wang, Chenguang

AU - Reutens, Anne T.

AU - Wang, Jian

AU - Angeletti, Ruth H.

AU - Siconolfi-Baez, Linda

AU - Ogryzko, Vasily

AU - Avantaggiati, Maria Laura

AU - Pestell, Richard G.

PY - 2000/7/7

Y1 - 2000/7/7

N2 - The androgen receptor (AR) is a sequence-specific DNA-binding protein that plays a key role in prostate cancer cellular proliferation by dihydrotestosterone and the induction of secondary sexual characteristics. In this study we demonstrate that the AR can be modified by acetylation in vitro and in vivo. p300 and p300/cAMP-response element-binding protein acetylated the AR at a highly conserved lysine-rich motif carboxyl-terminal to the zinc finger DNA-binding domain. [14C]acetate-labeling experiments demonstrated that AR acetylation by p300 in cultured cells requires the same residues identified in vitro. Point mutation of the AR acetylation site (K632A/K633A) abrogated dihydrotestosterone-dependent transactivation of the AR in cultured cells. Mutation of the p300 CH3 region or the p300/cAMP-response element- binding protein histone acetylase domain reduced ligand-dependent AR function. The identification of the AR as a direct target of histone acetyltransferase co-activators has important implications for targeting inhibitors of AR function.

AB - The androgen receptor (AR) is a sequence-specific DNA-binding protein that plays a key role in prostate cancer cellular proliferation by dihydrotestosterone and the induction of secondary sexual characteristics. In this study we demonstrate that the AR can be modified by acetylation in vitro and in vivo. p300 and p300/cAMP-response element-binding protein acetylated the AR at a highly conserved lysine-rich motif carboxyl-terminal to the zinc finger DNA-binding domain. [14C]acetate-labeling experiments demonstrated that AR acetylation by p300 in cultured cells requires the same residues identified in vitro. Point mutation of the AR acetylation site (K632A/K633A) abrogated dihydrotestosterone-dependent transactivation of the AR in cultured cells. Mutation of the p300 CH3 region or the p300/cAMP-response element- binding protein histone acetylase domain reduced ligand-dependent AR function. The identification of the AR as a direct target of histone acetyltransferase co-activators has important implications for targeting inhibitors of AR function.

UR - http://www.scopus.com/inward/record.url?scp=0034617058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034617058&partnerID=8YFLogxK

U2 - 10.1074/jbc.M000660200

DO - 10.1074/jbc.M000660200

M3 - Article

VL - 275

SP - 20853

EP - 20860

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 27

ER -