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Repression of androgen-regulated gene expression by dominant negative androgen receptors.

Abstract：

:The androgen receptor (AR) is a ligand-dependent transcription activator responsible for male sexual development. In order to specifically inhibit the AR pathway, dominant negative ARs were constructed by inactivation of the major transactivation domains of the wild type AR and fusing this mutant (AR122) to the Krüppel-associated box (KRAB) repressor domain and/or histone deacetylase (HDAC1). The HDAC1-KRAB-AR122 protein was the most successful dominant negative AR, capable of repressing the wild type AR ninefold when co-expressed at a 1:1 plasmid ratio. A maximal repression of 41-fold was achieved when HDAC1-KRAB-AR122 was cotransfected with the wild type AR at a 4:1 plasmid ratio. HDAC1-KRAB-AR122 repressed transcription in a ligand-dependent manner since it inhibited a constitutively active AR mutant (AR5) only in the presence of agonists. High concentrations of partial agonists such as RU486, cyproterone acetate, and estradiol were also capable of triggering repression by HDAC1-KRAB-AR122. The potent dominant negative AR proteins might prove useful tools to inhibit AR function in vitro and in vivo.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Bramlett KS,Dits NF,Sui X,Jorge MC,Zhu X,Jenster G

doi

10.1016/s0303-7207(01)00636-0

keywords:

subject

Has Abstract

pub_date

2001-10-25 00:00:00

pages

19-28

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(01)00636-0

journal_volume

183

pub_type

杂志文章

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