Nuclear Receptors        By: Dr. Vahid Nikoui    Email: nikoui@razi.tums.ac.ir
   Regulate gene expression   Ligands pass the cell membrane by simple    diffusion   Receptors in the cytoplasm or in ...
Small molecule coactivators of transcriptionSteroids
Small molecule coactivators oftranscriptionLipid-Soluble Vitamins & Thyroid Hormone                        Vitamin A Thyro...
Nuclear receptor ligands are structurally diverse   Steroids    – Estrogen (ER α,β)    – Progesterone (PR)    – Androgen ...
Steroid hormone    receptors
Action of Steroid Hormones versus              Peptide Hormones                           Peptide Hormones   SteroidsHalf-...
Steroid Receptor Action           Roles of Heat Shock Proteins and HREs            hsp90   hsp70                     H hsp...
Nuclear hormone receptor: domain structure                              Zinc finger                              DNA bindi...
Role of Phosphorylation in Steroid Receptor Activation          8-bromo cyclic AMP                                 PKA?   ...
HETERODIMERSCONTAINING RXR
T3 HORMONEVITAMIN D3ALL-TRANS RETINOIC ACID9-CIS RETINOIC ACID
Thyroid Hormone   Receptors
Thyroid hormone receptors
THANK YOU !
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
Nuclear Receptors
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Nuclear Receptors

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Nuclear Receptors

  1. 1. Nuclear Receptors By: Dr. Vahid Nikoui Email: nikoui@razi.tums.ac.ir
  2. 2.  Regulate gene expression Ligands pass the cell membrane by simple diffusion Receptors in the cytoplasm or in the nucleus
  3. 3. Small molecule coactivators of transcriptionSteroids
  4. 4. Small molecule coactivators oftranscriptionLipid-Soluble Vitamins & Thyroid Hormone Vitamin A Thyroid Hormone
  5. 5. Nuclear receptor ligands are structurally diverse Steroids – Estrogen (ER α,β) – Progesterone (PR) – Androgen (AR) Non-steroidal lipophilic hormones – 1, 25-(OH)2-vitamin D3 (VDR) – All- trans-retinoic acid (RAR α,β, γ) – 9-cis-retinoic acid (RXR α,β, γ) – Fatty acids (PPAR α,β, γ) – Thyroid hormone (TR α,β) Orphans (No ligand or ligand unknown)
  6. 6. Steroid hormone receptors
  7. 7. Action of Steroid Hormones versus Peptide Hormones Peptide Hormones SteroidsHalf-life in circulation short longSpeed of action fast slowDuration of effect short longLocation of receptor membrane insidePost-receptor regulation high lowSignal amplification high low
  8. 8. Steroid Receptor Action Roles of Heat Shock Proteins and HREs hsp90 hsp70 H hsp70 H H R hsp56 dimerize H H P? H H GeneTranscription HRE target gene 5’ flanking region
  9. 9. Nuclear hormone receptor: domain structure Zinc finger DNA binding domain… inserts into major groove of DNA
  10. 10. Role of Phosphorylation in Steroid Receptor Activation 8-bromo cyclic AMP PKA? + Phosphate hypervariable DBD HBD transcription
  11. 11. HETERODIMERSCONTAINING RXR
  12. 12. T3 HORMONEVITAMIN D3ALL-TRANS RETINOIC ACID9-CIS RETINOIC ACID
  13. 13. Thyroid Hormone Receptors
  14. 14. Thyroid hormone receptors
  15. 15. THANK YOU !

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