Nuclear Receptors Flashcards
(20 cards)
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
What is the androgen receptor responsible for and what does dysregulation of AR lead to?
- Male sexual differentiation, muscle homeostasis & development
- Pathogenesis of primary prostate cancer
What is the progesterone receptor responsible for and what does dysregulation of PR lead to?
- Development of mammary glands & female productive organs
- Prostate cancer progression
What is the oestrogen receptor responsible for and what does dysregulation of OR lead to?
- Female reproduction & development of sexual characteristics
- Breast cancer development & metastasis
What are The Retinoid X Receptors (RXRs) responsible for and what does downregulation of RXRs lead to?
- Lipid metabolism, apoptosis & immune system
- Downregulation promote inflammation of vital organ systems
What are The Peroxisome Proliferator activated receptors (PPARs) and what are they used to treat?
- Cellular differentiation, development & metabolism
- Ligands of PPAR enhance peripheral insulin sensitivity & used to treat type II diabetes
