9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor

Kuang Hsiang Chuang, Yi Fen Lee, Wen Jye Lin, Chin Yi Chu, Saleh Altuwaijri, Yu-Jui Yvonne Wan, Chawnshang Chang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Although the retinoic X receptor (RXR) forms heterodimers with many members of the estrogen receptor subfamily, the interaction between RXR and the members of the glucocorticoid receptor sub-family remains unclear. Here we show that the RXR can form a heterodimer with the androgen receptor (AR) under in vitro and in vivo conditions. Functional analyses further demonstrated that the AR, in the presence or absence of androgen, can function as a repressor to suppress RXR target genes, thereby preventing the RXR binding to the RXR DNA response element. In contrast, RXR can function as a repressor to suppress AR target genes in the presence of 9-cis-retinoic acid, but unliganded RXR can function as a weak coactivator to moderately enhance AR transactivation. Together, these results not only reveal a unique interaction between members of the two nuclear receptor subfamilies, but also represent the first evidence showing a nuclear receptor (RXR) may function as either a repressor or a coactivator based on the ligand binding status.

Original languageEnglish (US)
Pages (from-to)1200-1212
Number of pages13
JournalMolecular Endocrinology
Volume19
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Retinoid X Receptors
Androgen Receptors
Cytoplasmic and Nuclear Receptors
Glucocorticoid Receptors
Response Elements
Estrogen Receptors
Transcriptional Activation
Androgens
Genes
Ligands
alitretinoin

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor. / Chuang, Kuang Hsiang; Lee, Yi Fen; Lin, Wen Jye; Chu, Chin Yi; Altuwaijri, Saleh; Wan, Yu-Jui Yvonne; Chang, Chawnshang.

In: Molecular Endocrinology, Vol. 19, No. 5, 05.2005, p. 1200-1212.

Research output: Contribution to journalArticle

Chuang, Kuang Hsiang ; Lee, Yi Fen ; Lin, Wen Jye ; Chu, Chin Yi ; Altuwaijri, Saleh ; Wan, Yu-Jui Yvonne ; Chang, Chawnshang. / 9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor. In: Molecular Endocrinology. 2005 ; Vol. 19, No. 5. pp. 1200-1212.
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