The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity

Maofu Fu, Mahadev Rao, Kongming Wu, Chenguang Wang, Xueping Zhang, Mohamed Hessien, Yee Guide Yeung, Daniel Gioeli, Michael J. Weber, Richard G. Pestell

Research output: Contribution to journalArticle

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Abstract

The androgen receptor (AR) regulates ligand-dependent gene transcription upon binding specific DNA sequences. The AR conveys both trans-activation and trans-repression functions, which together contribute to prostate cellular growth, differentiation, and apoptosis. Like histone H3, the AR is post-translationally modified by both acetylation and phosphorylation. The histone acetyltransferase p300 transactivates the AR and directly acetylates the AR in vitro at a conserved motif. Point mutations of the AR acetylation motif that abrogate acetylation reduce trans-activation by p300 without affecting the trans-repression function of the AR. The current studies assessed the functional relationship between acetylation and phosphorylation of the AR. Herein trans-activation of the AR acetylation site mutants were enhanced by the p42/p44 MAPK pathway but were defective in regulation by protein kinase A (PKA) signaling. PKA inhibition augmented ARwt activity but not AR acetylation mutant gene reporter activity and association at an androgen response element in chromatin immunoprecipitation assays. Mutations of the lysine residues at the AR acetylation site reduced trichostatin A (TSA) responsiveness and ligand-induced phosphorylation of the AR. The AR acetylation site mutant formed ligand-induced phosphorylation-dependent isoforms with distinguishable characteristics from wild type AR as determined with two-dimensional electrophoresis. Conversely, point mutation of a subset of AR phosphorylation sites reduced trichostatin A responsiveness and trans-activation by histone acetyltransferases. Together these studies suggest that acetylation and phosphorylation of the AR are linked events and that the conserved AR lysine motif contributes to a select subset of pathways governing AR activity.

Original languageEnglish
Pages (from-to)29436-29449
Number of pages14
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
Publication statusPublished - 09-07-2004

Fingerprint

Acetylation
Androgen Receptors
Phosphorylation
trichostatin A
Chemical activation
Histone Acetyltransferases
Cyclic AMP-Dependent Protein Kinases
Ligands
Point Mutation
Lysine
Genes
Histamine H3 Receptors
Mitogen-Activated Protein Kinase 3

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fu, Maofu ; Rao, Mahadev ; Wu, Kongming ; Wang, Chenguang ; Zhang, Xueping ; Hessien, Mohamed ; Yeung, Yee Guide ; Gioeli, Daniel ; Weber, Michael J. ; Pestell, Richard G. / The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 28. pp. 29436-29449.
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Fu, M, Rao, M, Wu, K, Wang, C, Zhang, X, Hessien, M, Yeung, YG, Gioeli, D, Weber, MJ & Pestell, RG 2004, 'The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity', Journal of Biological Chemistry, vol. 279, no. 28, pp. 29436-29449. https://doi.org/10.1074/jbc.M313466200

The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity. / Fu, Maofu; Rao, Mahadev; Wu, Kongming; Wang, Chenguang; Zhang, Xueping; Hessien, Mohamed; Yeung, Yee Guide; Gioeli, Daniel; Weber, Michael J.; Pestell, Richard G.

In: Journal of Biological Chemistry, Vol. 279, No. 28, 09.07.2004, p. 29436-29449.

Research output: Contribution to journalArticle

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AU - Fu, Maofu

AU - Rao, Mahadev

AU - Wu, Kongming

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