Nuclear Receptors Flashcards
Where can you find Nuclear Receptors?
Inside the cell
What are some characteristics of Nuclear Receptors?
1) One receptor can stimulate many different gene expressions
2) Ligands and drugs are highly lipophilic
3) On-set of biological response is usually slow
4) Resting state can be located in both cytosol or in the nucleus
What are the 3 classes of Nuclear receptors?
Class I: Steroid Receptor Family
Hybrid Class: Thyroid/ Retinoid Receptor Family
Class II: Orphan Receptor Family
What are the structural features of steroid receptors?
Ligand binding domain
After binding;
DNA binding domain
Transcription activating domain
Forms a homodimer before binding to response element
What are examples of Class I Steroid Receptors and their ligands?
Glucocorticoid (Cortisol)
Mineralocorticoid (Aldosterone)
Estrogen (Estrone, Estradiol, Estriol)
Progesterone (Progesterone)
Androgen (Testosterone)
What is the mechanism of action of Steroid Receptors?
1) Ligand crosses the membrane and enters the cell
2) Binds to the nuclear receptor exposing the DNA and transcription binding regions
3) Forms a homodimer and enters nucleus
4) Binds to element on DNA within nucleus
Class I receptors all form homodimers
What are some examples of Hybrid class Thyroid/ Retinoid receptors and their ligands?
Thyroid Receptor (Triiodothyronine)
Vitamin D Receptor (1,25-di(OH) Vitamin D3)
All-Trans Retinoic acid receptor (All-trans retinoic acid; Vit A)
Retinoic X Receptor (9-cis Retinoic Acid or Alitretinoin; Vit A metabolite)
Hybrid Class receptors form heterodimers namely with RXR
What are some examples of Class II Orphan Nuclear Receptors and their ligands?
Peroxisome Proliferator-Activated Receptor (Lysophosphatidic acid[LPA], PGI2, LTB4)
Aryl Hydrocarbon Receptor (Bilurubin, Aromatic hydrocarbons [Eg. Benzo(a)pyrene => Carcinogenic], Dioxin)
What is the Mechanism for Carcinogenesis?
Constant activation of Nuclear receptors
Results in increased DNA proliferation
Alteration of Protein Expression
Examples of drugs to treat Carcinogenesis:
Fulvestrant (Selective Estrogen Receptor Degrader)
Apalutamid (Androgen Receptor Blocker)
Where are Class I Receptors found?
Mainly in the cytoplasm
Where are Hybrid Class Receptors generally found?
Mainly endocrine
Where are Class II receptors normally found?
In the nucleus
And they operate as a heterodimer with RXR except RXR (homodimer)
What are the 4 different modes of activation?
1) Genomic (Bind directly to DNA)
2) Tethered (Binds with transcription factors)
3) Non-genomic (Bind to GPCR)
4) Ligand-independent (Can be growth receptor instead of nuclear receptor ligand)
