Dependence of selective gene activation on the androgen receptor NH2- and COOH-terminal interaction

Bin He, Lori W. Lee, John T. Minges, Elizabeth M. Wilson

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

The agonist-induced androgen receptor NH2- and COOH-terminal (N/C) interaction is mediated by the FXXLF and WXXLF NH2-terminal motifs. Here we demonstrate that agonist-dependent transactivation of prostate-specific antigen (PSA) and probasin enhancer/promoter regions requires the N/C interaction, whereas the sex-limited protein gene and mouse mammary tumor virus long terminal repeat do not. Transactivation of PSA and probasin response regions also depends on activation function 1 (AF1) in the NH2-terminal region but can be increased by binding an overexpressed p160 co-activator to activation function 2 (AF2) in the ligand binding domain. The dependence of the PSA and probasin enhancer/promoters on the N/C interaction for transactivation allowed us to demonstrate that in the presence of androgen, the WXXLF motif with the sequence 433WHTLF437 contributes as an inhibitor to AR transactivation. We further show that like the FXXLF and LXXLL motifs, the WXXLF motif interacts in the presence of androgen with AF2 in the ligand binding domain. Sequence comparisons among species indicate greater conservation of the FXXLF motif compared with the WXXLF motif, paralleling the functional significance of these binding motifs. The data provide evidence for promoter-specific differences in the requirement for the androgen receptor N/C interaction and in the contributions of AF1 and AF2 in androgen-induced gene regulation.

Original languageEnglish (US)
Pages (from-to)25631-25639
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number28
DOIs
StatePublished - Jul 12 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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