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.