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This version published online on July 31, 2003
Molecular Endocrinology, doi:10.1210/me.2002-0384
Molecular Endocrinology Vol. 0, No. 2003 200203841-
doi:10.1210/me.2002-0384
Copyright © 2003 by the Endocrine Society.
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Submitted on November 19, 2002
Accepted on July 25, 2003

Activation Functions 1 and 2 of Nuclear Receptors: Molecular Strategies for Transcriptional Activation

Anette Wärnmark1*, Eckardt Treuter1, Anthony Wright1, and Jan-Åke Gustafsson1

1 Departments of BioSciences and Medical Nutrition, Novum, Karolinska Institutet, Sweden and Section for Natural Sciences, Södertörns Högskola, Sweden

* To whom correspondence should be addressed. E-mail: jan-ake.gustafsson{at}mednut.ki.se.

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 pre-initiation 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 pre-initiation 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 1 (AF-1), which resides in the N-terminal domain, and the ligand-dependent activation function 2 (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.
Key words: Nuclear receptor • Transcriptional activation • Activation domain • Coactivators • Structure • Conformation • Protein-protein interaction

NURSA Molecule Pages Link:

Nuclear Receptors:   TRα  |  TRβ  |  PPARγ  |  VDR  |  HNF4α  |  RXRα  |  RXRγ  |  ERα  |  ERβ  |  GR  |  MR  |  PR  |  NURR1
Coregulators:   TRAP220  |  CBP  |  DRIP150  |  GRIP1



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