nuclear receptor 2009 - Mechanism of Atrazine Action...

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atrazine cyclic nucleotide phosphodiesterase (PDE) (enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP) cAMP levels increase SF-1 (a member of nuclear receptor family; transcription factor; highly expressed in adrenal and sexual organs) Aromatase gene transcription increases Mechanism of Atrazine Action PLoS One. 2008 May 7;3(5):e2117.
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Nuclear Receptors -nuclear receptors are a class of proteins found within the interior of cells that are responsible for sensing the presence of hormones and certain lipophilic molecules. There are 48 NHRs in human genome Ajay Chawla, Joyce J. Repa, Ronald M. Evans, David J. Mangelsdorf; Science 30 November 2001: Vol. 294. no. 5548, pp. 1866 - 1870
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-DBD is most conserved among NRs. DBD contains two zinc fingers that make contacts with DNA. -LBD binds to specific lipophilic molecules. -A/B (AF1) and F (AF2) are usually transactivation domain. AF2 activity is usually dependent on ligands.
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Type I NR: Steroid Receptors: GR (glucocorticoids), MR(mineralcorticoids), AR (androgen), PR (progesterone) usually locate at cytoplasm before binding to ligands. ER (estrogen) is located in nucleus. -receptors associate with heat shock protein 90 chaperone complex in cytoplasm. -binding to ligands allows receptors to dissociate from hsp90 complex and enter nucleus. -binding to specific DNA sequences (as a homodimer): hormone response element (HRE,inverted repeats), and regulate gene transcription.
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Type II NR: TR (thyroid hormones), RAR (retinoic acids), VDR (vitamin D) and some orphan receptors (CAR, PPARs, LXR, FXR, PXR/SXR…). -receptor locates in nucleus before binding to ligands; receptor sit at the HREs as a heterodimer with RXR (9-cis retinoic acid Receptor). -without ligands, NR-RXR recruits transcriptional corepressors to suppress gene transcription.
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nuclear receptor 2009 - Mechanism of Atrazine Action...

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