Nuclear Receptors Flashcards
What are nuclear receptors?
A superfamily of intracellular DNA-binding transcription factors that selectively bind small-molecule lipophilic ligands, and transduce their signals into specific changes in gene expression
Where are they located?
In the cytosol or nucleus
They translocate to the nucleus upon ligand binding
How many members does the human superfamily consist of?
48
They regulate cell differentiation, proliferation & metabolism
NRs are _____ proteins that consist of __ main domains
monomeric proteins
5
Name the 5 domains
- N-terminal (A/B) domain (NTD)
- DNA-binding (C) domain (DBD)
- Hinge (D) region
- Ligand-binding (E) domain (LBD)
- C-terminal (F) domain
Name the 2 groups depending on identification of endogenous ligands
1) Endocrine NRs (ligands identified)
2) Orphan NRs (ligands unknown)
Name the 4 classes
1) Class I (Steroid Receptors/Nuclear Hormone Receptors)
2) Class II (RXR Heterodimers)
3) Class III (Dimeric Orphan Receptors)
4) Class IV (Monomeric Orphan Receptors)
What are Steroid Receptors?
Located in cytoplasm as monomers bound to chaperone proteins, ligand-activated homo-dimerize
What are RXR heterodimers?
Receptors for thyroid hormones, vit A metabolites & vit D
Heterodimers are bound to _______ even in the absence of their ligands
specific DNA
What are non-permissive complexes?
Require binding of ligands for BOTH partners for activation
What are permissive complexes?
Require binding of ligand for EITHER partner for activation
What do Class I NRs play unique roles in ?
- Maintenance of cellular homeostasis
- Regulation of gene expression in embryogenesis & tissue development
What do Class II NRs play important role in?
- Lipid metabolism
- Cell proliferation
- Differentiation
- Adipogenesis & inflammatory signalling
What can dysregulation lead to?
Systemic organ dysfunction and diseases
