PT  - JOURNAL ARTICLE
AU  - Fu, Maofu
AU  - Rao, Mahadev
AU  - Wang, Chenguang
AU  - Sakamaki, Toshiyuki
AU  - Wang, Jian
AU  - Di Vizio, Dolores
AU  - Zhang, Xueping
AU  - Albanese, Chris
AU  - Balk, Steven
AU  - Chang, Chawnshang
AU  - Fan, Saijun
AU  - Rosen, Eliot
AU  - Palvimo, Jorma J.
AU  - Jänne, Olli A.
AU  - Muratoglu, Selen
AU  - Avantaggiati, Maria Laura
AU  - Pestell, Richard G.
TI  - Acetylation of Androgen Receptor Enhances Coactivator Binding and Promotes Prostate Cancer Cell Growth
AID  - 10.1128/MCB.23.23.8563-8575.2003
DP  - 2003 Dec 01
TA  - Molecular and Cellular Biology
PG  - 8563--8575
VI  - 23
IP  - 23
4099  - http://mcb.asm.org/content/23/23/8563.short
4100  - http://mcb.asm.org/content/23/23/8563.full
SO  - Mol. Cell. Biol.2003 Dec 01; 23
AB  - Modification by acetylation occurs at ε-amino lysine residues of histones and transcription factors. Unlike phosphorylation, a direct link between transcription factor acetylation and cellular growth or apoptosis has not been established. We show that the nuclear androgen receptor (AR), a DNA-binding transcriptional regulator, is acetylated in vivo. The acetylation of the AR is induced by ligand dihydrotestosterone and by histone deacetylase (HDAC) inhibitors in living cells. Direct AR acetylation augmented p300 binding in vitro. Constructs mimicking neutral polar substitution acetylation (ARK630Q, ARK630T) enhanced p300 binding and reduced N-CoR/HDAC/Smad3 corepressor binding, whereas charged residue substitution (ARK630R) reduced p300 binding and enhanced corepressor binding. The AR acetylation mimics promoted cell survival and growth of prostate cancer cells in soft agar and in nude mice and augmented transcription of a subset of growth control target gene promoters. Thus, transcription factor acetylation regulates coactivator/corepressor complex binding, altering expression of specific growth control genes to promote aberrant cellular growth in vivo.