MODULE 8: Chapter 8.5

Question 1

What are nuclear receptors also known as?

Answer 1

Intracellular receptors

Question 2

What is the primary function of nuclear receptors?

Answer 2

Regulate gene expression in response to ligand binding

Question 3

What are the three parameters that govern the physiologic responses controlled by nuclear receptors?

Answer 3

• Cell-specific expression of nuclear receptors and/or coregulatory proteins
• Localized bioavailability of ligands
• Differential accessibility of target gene DNA sequences in chromatin

Question 4

What does GR stand for in nuclear receptor terminology?

Answer 4

Glucocorticoid receptor

Question 5

What is the function of the glucocorticoid receptor?

Answer 5

Binds steroid hormones

Question 6

What is the glucocorticoid response element abbreviated as?

Answer 6

GRE

Question 7

What role does Hsp90 play in nuclear receptor signaling?

Answer 7

Assists protein folding

Question 8

What does PPAR stand for?

Answer 8

Peroxisome proliferator–activated receptor

Question 9

What is the role of RXR in nuclear receptor signaling?

Answer 9

Binding partner of most metabolite nuclear receptors

Question 10

What are the two main types of nuclear receptors?

Answer 10

• Steroid receptors
• Metabolite receptors

Question 11

True or False: Steroid receptors bind to direct repeat DNA sequences as homodimers.

Answer 11

False

Question 12

What is the consensus sequence for steroid receptors?

Answer 12

5′-AGAACA-3′

Question 13

What types of ligands do steroid receptors bind?

Answer 13

Physiologic hormones derived from cholesterol

Question 14

What is the consensus sequence for metabolite receptors?

Answer 14

5′-AGGTCA-3′

Question 15

What types of ligands do metabolite receptors typically bind?

Answer 15

Dietary nutrients, including vitamins and unsaturated fatty acids

Question 16

Fill in the blank: The glucocorticoid receptor is a _______ protein expressed in various cell types.

Answer 16

90-kDa

Question 17

What physiological role do glucocorticoids play in the body?

Answer 17

Modulate the inflammatory response and carbohydrate metabolism

Question 18

What is the primary anti-inflammatory action of glucocorticoids mediated by GR?

Answer 18

Inducing the expression of annexin I

Question 19

What does NFκB stand for?

Answer 19

Nuclear factor kappa-light-chain-enhancer of activated B cells

Question 20

What is the effect of ligand-activated GR on NFκB?

Answer 20

Inhibits its transcriptional regulatory functions

Question 21

What is the binding affinity of pharmaceutical glucocorticoids compared to cortisol?

Answer 21

Higher than that of cortisol

Question 22

What is the role of heat shock protein 90 (Hsp90) in relation to GR?

Answer 22

Part of the GR–chaperonin complex in the cytoplasm

Question 23

True or False: The unliganded GR protein resides in the nucleus.

Answer 23

False

Question 24

What happens to the GR–chaperonin complex upon ligand binding?

Answer 24

Disassembly occurs

Question 25

What is the relationship between ligand binding and transcriptional regulation by nuclear receptors?

Answer 25

Transcriptional regulatory functions are ligand regulated

Question 26

What is the role of heat shock protein 90 (Hsp90)?

Answer 26

Hsp90 is a chaperonin protein that assists in protein folding.

Question 27

What happens when ligand binds to glucocorticoid receptor (GR)?

Answer 27

Ligand binding results in disassembly of the GR–chaperonin complex and translocation of GR into the nucleus.

Question 28

Where does the glucocorticoid receptor (GR) bind in the nucleus?

Answer 28

GR homodimers bind to glucocorticoid response elements (GREs) in the regulatory region of the annexin I gene.

Question 29

What is the effect of monomers of ligand-activated GR on NFκB?

Answer 29

Monomers bind to the p65 subunit of NFκB, inhibiting its transcriptional regulatory activity.

Question 30

What is the outcome of GR signaling in target cells?

Answer 30

The net result is reduced inflammation.

Question 31

Why do the beneficial effects of pharmaceutical steroids take several days to manifest?

Answer 31

Gene transcription, RNA processing, and protein accumulation take time.

Question 32

What contributes to the long-lasting effects of steroid treatment?

Answer 32

Decreased steroid levels reduce gene expression slowly and steroids accumulate in nonpolar compartments.

Question 33

What is the affinity of dexamethasone for the glucocorticoid receptor compared to cortisol?

Answer 33

Dexamethasone has an affinity 50 times higher than cortisol.

Question 34

Define 'coregulatory protein'.

Answer 34

Coregulatory proteins, also called coactivators or corepressors, modulate transcription rates by interacting with ligand-activated nuclear receptors.

Question 35

What defines a steroid receptor?

Answer 35

A class of nuclear receptor proteins activated by physiologic hormones derived from cholesterol.

Question 36

What is a metabolite receptor?

Answer 36

A type of nuclear receptor activated by ligands derived from dietary nutrients.

Question 37

What is the function of the retinoid X receptor (RXR)?

Answer 37

RXR is a heterodimeric binding partner that facilitates binding to direct repeat sequences of DNA.

Question 38

What is the role of steroid receptor coactivators (SRC)?

Answer 38

SRC is a family of nuclear receptor coregulatory proteins.

Question 39

What is the function of a chaperonin protein?

Answer 39

Chaperonin proteins assist in protein folding.

Question 40

What is the role of peroxisome proliferator–activated receptor (PPAR)?

Answer 40

PPAR is a member of the nuclear receptor superfamily characterized as a metabolite receptor.

Question 41

What are glucocorticoid response elements (GREs)?

Answer 41

GREs are DNA cis-acting sequences located near glucocorticoid-regulated genes that serve as binding sites for ligand-activated GRs.

Question 42

Fill in the blank: The _______ is involved in many pathways including nuclear receptor signaling.

Answer 42

heat shock protein 90 (Hsp90)