Selective DNA recognition by the androgen receptor as a mechanism for hormone-specific regulation of gene expression
Abstract
The androgen receptor (AR) is a member of the highly conserved group of the class I steroid hormone receptors, a subgroup of the nuclear receptor superfamily of ligand-induced transcription factors. All class I receptors influence the expression of their target genes by binding three-nucleotide spaced partial palindromic repeats of the core 5'-TGTTCT-3' motif. The implication that all class I receptors activate transcription by binding similar DNA motifs, poses the problem of how the in vivo steroid-specificity of transcriptional control is achieved. The AR, however, is able to interact with DNA motifs that are divergent from the classical hormone response elements. We will describe this AR-specific DNA interaction in the context of the general mechanisms that dictate the sequence-specificity of DNA-binding and dimerization of the nuclear receptors. The androgen receptor is the only steroid hormone receptor that is able to interact with response elements that are essentially arranged as a direct repeat of the 5'-TGTTCT-3' monomer binding element. We propose that the DNA-binding domain of the AR can interact with these androgen-specific response elements in a head-to-tail conformation, similar to many other nuclear hormone receptors. The fact that subtle differences in the sequence of response elements can dictate androgen-specific responses is a new and intriguing finding. It creates new possibilities in the research on hormone-selective action and provides a new angle in the search for selective ligands or co-factors that might influence androgen receptor action via either type of DNA motif.
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In skin, androgens act through androgen receptors to trigger signaling cascades.
“In skin, androgens mediate their effects through interaction with the androgen receptors (AR) triggering cascades of networks [91, 106, 187–189].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [187]
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- Authors
- Verrijdt, G.
- Affiliations
- KU Leuven (BE)
- Corresponding author
- Verrijdt, G
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 78
- Issue
- 3
- Pages
- 175-185
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W1976983409
- Cited by
- 148
- References
- 5
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 9 · 2015: 6 · 2014: 3 · 2013: 12 · 2012: 5
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Genetics and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- androgen receptor, DNA binding specificity, hormone response elements, selective ligands, cofactors
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, DNA, Gene Expression Regulation, Humans, Molecular Sequence Data, Receptors, Androgen, Substrate Specificity
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