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Activation Functions 1 and 2 of Nuclear Receptors: Molecular Strategies for Transcriptional Activation
Open accessAbstract
Nuclear receptors (NRs) comprise a family of ligand inducible transcription factors. To achieve transcriptional activation of target genes, DNA-bound NRs directly recruit general transcription factors (GTFs) to the preinitiation complex or bind intermediary factors, so-called coactivators. These coactivators often constitute subunits of larger multiprotein complexes that act at several functional levels, such as chromatin remodeling, enzymatic modification of histone tails, or modulation of the preinitiation complex via interactions with RNA polymerase II and GTFs. The binding of NR to coactivators is often mediated through one of its activation domains. Many NRs have at least two activation domains, the ligand-independent activation function (AF)-1, which resides in the N-terminal domain, and the ligand-dependent AF-2, which is localized in the C-terminal domain. In this review, we summarize and discuss current knowledge regarding the molecular mechanisms of AF-1- and AF-2-mediated gene activation, focusing on AF-1 and AF-2 conformation and coactivator binding.
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“The transcriptional activation functions of the receptors reside in both the NTD (a constitutively active AF-1) and LBD (a ligand-dependent AF-2), through which essential coactivators usually are recruited with DNA-bound receptors to activate transcription (Warnmark et al., 2003).”
From Structural Insights of Transcriptionally Active, Full-Length Androgen Receptor Coactivator Complexes (2020) · cites this paper as Warnmark et al., 2003
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Metadata
- Authors
- Wärnmark, A., Treuter, E., Wright, A. P. H., & Gustafsson, J.-A.
- Affiliations
- Departments of BioSciences (A.W., E.T., A.P.H.W., J.-Å.G.), S-141 89 Huddinge, Sweden
- Södertörn University (SE)
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-10-01
- Volume
- 17
- Issue
- 10
- Pages
- 1901-1909
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W1964247670
- Cited by
- 308
- References
- 99
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 10 · 2023: 16 · 2022: 20 · 2021: 10 · 2020: 16 · 2019: 14 · 2018: 7 · 2017: 14 · 2016: 11 · 2015: 11 · 2014: 20 · 2013: 12 · 2012: 17
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Karolinska Institutet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- nuclear receptors, activation functions, AF-2, transcriptional activation, transcriptional coactivator, general transcription factors, preinitiation complex, chromatin remodeling, histone modifications, RNA polymerase II, ligand-independent receptor activation, ligand-dependent activation
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Receptors, Cytoplasmic and Nuclear
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