Activation Functions 1 and 2 of Nuclear Receptors: Molecular Strategies for Transcriptional Activation
- 1 October 2003
- journal article
- review article
- Published by The Endocrine Society in Molecular Endocrinology
- Vol. 17 (10), 1901-1909
- https://doi.org/10.1210/me.2002-0384
Abstract
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.Keywords
This publication has 80 references indexed in Scilit:
- Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF MotifsMolecular and Cellular Biology, 2003
- Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonismNature Structural & Molecular Biology, 2002
- How Transcriptional Activators Bind Target ProteinsPublished by Elsevier BV ,2001
- Differential Recruitment of the Mammalian Mediator Subunit TRAP220 by Estrogen Receptors ERα and ERβPublished by Elsevier BV ,2001
- Functional Interactions between the Estrogen Receptor and DRIP205, a Subunit of the Heteromeric DRIP Coactivator ComplexPublished by Elsevier BV ,2000
- Architectural Principles for the Structure and Function of the Glucocorticoid Receptor τ1 Core Activation DomainPublished by Elsevier BV ,2000
- Structure and specificity of nuclear receptor–coactivator interactionsGenes & Development, 1998
- Structural motifs at protein‐protein interfaces: Protein cores versus two‐state and three‐state model complexesProtein Science, 1997
- Structural Studies of Mutant Glucocorticoid Receptor Transactivation Domains Establish a Link between Transactivation Activity in Vivo and α-Helix-Forming Potential in VitroBiochemistry, 1996
- Crystal structure of the RAR-γ ligand-binding domain bound to all-trans retinoic acidNature, 1995