Abstract

The androgen receptor (AR) is a nuclear transcription factor that is essential for development of the male urogenital tract. In the current work, we have characterized the mouse androgen receptor suppressor (mARS). A single, 20-base pair, region (TCCCCCCACCCACCCCC-CCT) was sufficient for suppression in chloramphenicol acetyltransferase assays. Northern analysis indicated that translational regulation is not necessary for the suppression. Analysis of the AR mRNA half-life indicated that the mARS does not affect AR RNA degradation. Gel mobility assays showed that the mARS is bound by multiple proteins that can recognize single-stranded DNA and RNA. In addition, differing proteins are expressed in distinct tissues. Purification of some of these proteins has shown that a doublet of 33 and 35 kDa binds to the G-rich strand and that a 52-kDa protein binds to the C-rich strand. Southwestern blots have confirmed that these proteins are indeed recognized by the mARS. The results of these experiments indicate that the AR 5'-untranslated region contains a suppressor element that can be bound by multiple proteins. The mARS appears to be acting either by altering transcription initiation or blocking transcription elongation. Characterization of this suppressor may provide insight into the physiological means by which the AR is regulated.

Highlights

  • The androgen receptor (AR) is a nuclear transcription factor that is essential for development of the male urogenital tract

  • Analysis of the AR mRNA half-life indicated that the mouse androgen receptor suppressor (mARS) does not affect AR RNA degradation

  • The results of these experiments indicate that the AR 5'-untranslated region contains a suppressor element that can be bound by multiple proteins

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Summary

THE JOURNAL OF BIOLOGICAL CHEMISTRY

Vol 270, No 18, Issue of May 5, pp. 10968-10975, 1995 Printed in U.S.A. The Androgen Receptor Is Transcriptionally Suppressed by Proteins That Bind Single-stranded DNA*. We have characterized the mouse androgen receptor suppressor (mARS). Southwestern blots have confirmed that these proteins are recognized by the mARS The results of these experiments indicate that the AR 5'-untranslated region contains a suppressor element that can be bound by multiple proteins. It was shown using CAT assays that the 5'-untranslated region of the AR contains a cis-acting suppressor element that was termed the mouse androgen receptor suppressor (mARS). The AR is essential during development and maintenance of the male urogenital organs and has been implicated in a number of diseases It is expressed at a relatively low level and has been shown to be regulated in a very complex manner that is dependent on both tissue and developmental effects (1).

EXPERIMENTAL PROCEDURES
Per cent Acti v it y
RES ULTS
Radioac tive Probe Lan e
Competito r i
DISCUSSI ON
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