Topic 4 - Nuclear Receptors and Apoptosis

Question 1

HRE

Answer 1

Hormone response element

Question 2

Nuclear receptors have 2 things, what are they?

Answer 2

1. Soluble receptors

2. Regulate transcription (acts as HRE)

Question 3

The large super family of nuclear receptors are divided by structure into 3 groups, what are they?

Answer 3

1. Steroid receptor family (GR, MR, AR, PR)
2. Thyroid receptor family (TR, ER, RAR, RXR, PPAR, VDR)
3. > 100 orphan receptors

Question 4

Where are steroid receptors stored?

Answer 4

In the cytoplasm

Question 5

Where are thyroid receptors stored?

Answer 5

In the nucleus

Question 6

GR

Answer 6

Glucocorticoid receptor (blood glucose-stress)

Question 7

MR

Answer 7

Mineralocorticoids (Na/K)

Question 8

AR

Answer 8

Androgen receptor (male sex; binds testosterone or dihydrotestosterone)

Question 9

PR

Answer 9

Progesterone receptor (supports pregnancy/embryogenesis)

Question 10

TR

Answer 10

Thyroid hormone receptor (development/metabolism/heart rate)

Question 11

ER

Answer 11

Estrogen receptor (female sex)

Question 12

RAR

Answer 12

Retinoic acid receptor (retinoids (vit A)/vision/cell cycle/immunity)

Question 13

RXR

Answer 13

Retinoic x receptor (heterodimer with other receptors in this family plus binds retinoids)

Question 14

PPAR

Answer 14

Peroxisome proliferator-activated receptor (developmental/metabolism)

Question 15

VDR

Answer 15

Vitamin D receptor (Ca/P/developmental) - helps in the immune function

Question 16

Steroid receptor signalling steps (4)

Answer 16

1. Steroid hormone diffuses across membrane
2. Hormone binding releases HSP and exposes NLS and dimerization occurs
3. Hormone-receptor complex transported into nucleus
4. Hormone-receptor complex binds to HRE and activates transcription

Question 17

HSP

Answer 17

Heat shock protein

Question 18

NLS

Answer 18

Nuclear localization signal

Question 19

When do HSP dimerize?

Answer 19

When they are bound to NLS

Question 20

What are the 3 basic domains that are important for nuclear receptors

Answer 20

1. Amino terminal domain
2. DNA binding domain
3. Ligand binding domain

Question 21

What is the function of the amino terminal domain?

Answer 21

Ligand-independent transactivation

Question 22

What are the functions of the DNA binding domain? (2)

Answer 22

1. DNA binding

2. Dimerization

Question 23

What are the functions of the ligand binding domain? (5)

Answer 23

1. Hetero- and homo- dimerization
2. Ligand binding
3. Ligand-dependent transactivation
4. Nuclear translocation
5. Association with heat shock proteins

Question 24

Which receptor acts alone?

Answer 24

TH receptor

Question 25

Which ligands act alone? (3)

Answer 25

1. Non-genomic ligands
2. Steroid ligands
3. TH ligands

Question 26

AF 1 or 2

Answer 26

Activation function 1 or 2

Question 27

What kind of structure does zinc adopt when it binds?

Answer 27

A planar structure

Question 28

What does diethylstibesterol mimic for binding and changes the conformation when you have a co-activator in place?

Answer 28

Estrogen

Question 29

What does structure mousetrap in phobic pocket allow for?

Answer 29

Co-activator binding

Question 30

Corepression and coactivation of nuclear receptor steps (3)

Answer 30

1. Corepressor complex HDACs close chromatin, repressing transcription
2. Ligand binds and ATP used to remodel chromatin
   3a. Coactivators recruit HATs, opens chromatin for transcription
   3b. Large coactivator complexes for TR and VDR bridge with basal transcription machinery

Question 31

HDAC

Answer 31

Histone deacetylasses

Question 32

BBP

Answer 32

Blood binding proteins

Question 33

What do BBP do? (2)

Answer 33

1. Transports hormones

2. Controlled release

Question 34

What is apoptosis?

Answer 34

Programmed cell death leading to dissolution of a cell and then phagocytosis of apoptotic bodies by macrophages

Question 35

What are 2 biological features associated with cell death?

Answer 35

1. DNA fragmentation

2. Alteration of membrane lipid compartmentalization

Question 36

What type of cells are associated with cell death?

Answer 36

Oncogenes

Question 37

What is Bcl-2?

Answer 37

It is a suppressor of death rather than a promoter of proliferation

Question 38

What does p53 tumor suppressor promote?

Answer 38

Cell death