nuclear hormone receptors
Sunday 23 November 2003
Members of the nuclear receptor family share several structural features, including a central, highly conserved DNA-binding domain (DBD) that targets the receptor to specific DNA sequences, termed hormone response elements.
The C-terminal portion of the receptor includes the ligand-binding domain (LBD), which interacts directly with the hormone and contains a hormone-dependent transcriptional activation domain.
The LBD serves as a molecular switch that recruits coactivator proteins and activates the transcription of target genes when flipped into the active conformation by hormone binding (Kliewer et al., 1999).
Nuclear hormone receptors comprise a large family of proteins that shares a common structure and mechanism of action. Members of this family are regulated by small lipophilic signaling molecules such as steroid hormones, retinoids and thyroid hormone.
NRs are comprised of: an amino-terminal activation function domain AF-1; the DNA-binding domain; a hinge region; and a carboxy-terminal ligand-binding domain containing a second activation function, AF-2.
VDR acts primarily as a heterodimer with the retinoid X receptor (RXR) on vitamin D response elements (VDREs). It interacts with the transcription machinery and nuclear receptor coactivators or corepressors to regulate target gene activity.
NRs coregulators can be divided into 3 major classes:
1)ATP-dependent chromatin remodeling complexes that are involved in the location and association of nucleosomes with DNA;
2) Enzymes that catalyze modifications of histone tails to regulate histone-histone and histone-DNA interactions;
nuclear receptors (NRs)