MODULE 8: Chapter 8.5 Flashcards
What are nuclear receptors also known as?
Intracellular receptors
What is the primary function of nuclear receptors?
Regulate gene expression in response to ligand binding
What are the three parameters that govern the physiologic responses controlled by nuclear receptors?
- Cell-specific expression of nuclear receptors and/or coregulatory proteins
- Localized bioavailability of ligands
- Differential accessibility of target gene DNA sequences in chromatin
What does GR stand for in nuclear receptor terminology?
Glucocorticoid receptor
What is the function of the glucocorticoid receptor?
Binds steroid hormones
What is the glucocorticoid response element abbreviated as?
GRE
What role does Hsp90 play in nuclear receptor signaling?
Assists protein folding
What does PPAR stand for?
Peroxisome proliferator–activated receptor
What is the role of RXR in nuclear receptor signaling?
Binding partner of most metabolite nuclear receptors
What are the two main types of nuclear receptors?
- Steroid receptors
- Metabolite receptors
True or False: Steroid receptors bind to direct repeat DNA sequences as homodimers.
False
What is the consensus sequence for steroid receptors?
5′-AGAACA-3′
What types of ligands do steroid receptors bind?
Physiologic hormones derived from cholesterol
What is the consensus sequence for metabolite receptors?
5′-AGGTCA-3′
What types of ligands do metabolite receptors typically bind?
Dietary nutrients, including vitamins and unsaturated fatty acids
Fill in the blank: The glucocorticoid receptor is a _______ protein expressed in various cell types.
90-kDa
What physiological role do glucocorticoids play in the body?
Modulate the inflammatory response and carbohydrate metabolism
What is the primary anti-inflammatory action of glucocorticoids mediated by GR?
Inducing the expression of annexin I
What does NFκB stand for?
Nuclear factor kappa-light-chain-enhancer of activated B cells
What is the effect of ligand-activated GR on NFκB?
Inhibits its transcriptional regulatory functions
What is the binding affinity of pharmaceutical glucocorticoids compared to cortisol?
Higher than that of cortisol
What is the role of heat shock protein 90 (Hsp90) in relation to GR?
Part of the GR–chaperonin complex in the cytoplasm
True or False: The unliganded GR protein resides in the nucleus.
False
What happens to the GR–chaperonin complex upon ligand binding?
Disassembly occurs
What is the relationship between ligand binding and transcriptional regulation by nuclear receptors?
Transcriptional regulatory functions are ligand regulated
What is the role of heat shock protein 90 (Hsp90)?
Hsp90 is a chaperonin protein that assists in protein folding.
What happens when ligand binds to glucocorticoid receptor (GR)?
Ligand binding results in disassembly of the GR–chaperonin complex and translocation of GR into the nucleus.
Where does the glucocorticoid receptor (GR) bind in the nucleus?
GR homodimers bind to glucocorticoid response elements (GREs) in the regulatory region of the annexin I gene.
What is the effect of monomers of ligand-activated GR on NFκB?
Monomers bind to the p65 subunit of NFκB, inhibiting its transcriptional regulatory activity.
What is the outcome of GR signaling in target cells?
The net result is reduced inflammation.
Why do the beneficial effects of pharmaceutical steroids take several days to manifest?
Gene transcription, RNA processing, and protein accumulation take time.
What contributes to the long-lasting effects of steroid treatment?
Decreased steroid levels reduce gene expression slowly and steroids accumulate in nonpolar compartments.
What is the affinity of dexamethasone for the glucocorticoid receptor compared to cortisol?
Dexamethasone has an affinity 50 times higher than cortisol.
Define ‘coregulatory protein’.
Coregulatory proteins, also called coactivators or corepressors, modulate transcription rates by interacting with ligand-activated nuclear receptors.
What defines a steroid receptor?
A class of nuclear receptor proteins activated by physiologic hormones derived from cholesterol.
What is a metabolite receptor?
A type of nuclear receptor activated by ligands derived from dietary nutrients.
What is the function of the retinoid X receptor (RXR)?
RXR is a heterodimeric binding partner that facilitates binding to direct repeat sequences of DNA.
What is the role of steroid receptor coactivators (SRC)?
SRC is a family of nuclear receptor coregulatory proteins.
What is the function of a chaperonin protein?
Chaperonin proteins assist in protein folding.
What is the role of peroxisome proliferator–activated receptor (PPAR)?
PPAR is a member of the nuclear receptor superfamily characterized as a metabolite receptor.
What are glucocorticoid response elements (GREs)?
GREs are DNA cis-acting sequences located near glucocorticoid-regulated genes that serve as binding sites for ligand-activated GRs.
Fill in the blank: The _______ is involved in many pathways including nuclear receptor signaling.
heat shock protein 90 (Hsp90)
