Nuclear Receptor Signaling

Question 1

All nuclear receptors will have a variable region, a [2] domain, and a [3] domain.

Answer 1

[1] DNA-binding

[2] ligand-binding

Question 2

Type 1 nuclear receptors will bind to [1].

Type 2 receptors will bind to [2].

Answer 2

[1] steroid hormones

[2] non-steroid ligands

Question 3

Type 1 receptors will bind to [1] consensus elements of DNA.

Type 2 receptors will bind to [2] consensus elements of DNA.

Answer 3

[1] inverted repeats (complementary strands)

[2] direct repeats (same strand)

Question 4

Type I nuclear receptors are kept in their monomeric un-ligated form in the [1] kept inactivated by a bound Hsp inhibitor.
Ligand (steroid) binds to ligand-binding domain and replaces Hsp.
Dimerization and binding to [2] sequences.

Answer 4

[1] cytosol
[2] inverted repeat
– enters nucleus // response element

Question 5

Type II nuclear receptors are already bound to DNA in the nucleus. It is also bound via a heterodimer called [1].
The binding of the ligand (direct repeats) leads to a association of the heterodimer away from the [2].

Answer 5

[1] RXR
[2] corepressor
– turns into coactivator

Question 6

does NOT work in ER (-) breast cancers

Answer 6

[1] Tamoxifen

– competitive inhibitor of the estrogen receptor

Question 7

Tamoxifen can actually bind to the estrogen receptor in [1] and stimulate signaling.
This is an increased cancer-risk side effect.

Answer 7

[1] uterine endometrial cells

Question 8

During a check-up a 56 year old man had elevated serum levels of prostate specific antigen (PSA).
PSA is regulated by [1].

Answer 8

[1] androgen receptors

Question 9

Prostate Cancer is treated with a method called [1].
Testicles: [2] agonists. Injectable. Blocks further androgen synthesis.
Adrenals: blocked by [3] drugs. Oral medication. Competes for AR.

Answer 9

[1] Androgen Ablation Therapy
[2] LHRH (LUPRON or ZOLADEX)
[3] anti-androgen (FLUTAMIDE or CASODEX)