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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Short heterodimer partner ( SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator ( ARNT).

SHP (short heterodimer partner) is an orphan nuclear receptor lacking a DNA binding domain that interacts with nuclear receptors (NR) including thyroid receptor (TR), retinoic acid receptors ( RAR and RXR), and estrogen receptors alpha and beta (ERalpha and ERbeta). SHP acts as a negative regulator of these receptors by inhibiting DNA binding and transcriptional activation. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) binds to arylhydrocarbon receptor ( AHR), activating the AHR/ AHR nuclear translocator ( ARNT) heterodimer. We investigated the physical and functional interaction of SHP with AHR/ ARNT. In RL95-2 human endometrial carcinoma cells, SHP inhibited TCDD- stimulated reporter activity from the AHR-responsive CYP1A1 and UGT1A6 gene promoters in a concentration-dependent manner. In GST pull-down assays, ARNT interacted directly with SHP in vitro, but AHR did not interact with GST- SHP. SHP inhibited AHR/ARNT-DNA binding in vitro. These results identify ARNT as a novel SHP target. We speculate a role for SHP in the suppression of agonist- activated AHR/ ARNT activity.[1]

References

  1. Short heterodimer partner (SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT). Klinge, C.M., Jernigan, S.C., Risinger, K.E., Lee, J.E., Tyulmenkov, V.V., Falkner, K.C., Prough, R.A. Arch. Biochem. Biophys. (2001) [Pubmed]
 
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