title: Expression of Ski can act as a negative feedback mechanism on retinoic acid signaling.
abstract: BACKGROUND
  Retinoic acid signaling is essential for many aspects of early development in vertebrates. To control the levels of signaling, several retinoic acid target genes have been identified that act to suppress retinoic acid signaling in a negative feedback loop. The nuclear protein Ski has been extensively studied for its ability to suppress transforming growth factor-beta (TGF-β) signaling but has also been implicated in the repression of retinoic acid signaling.
  
  
  RESULTS
  We demonstrate that ski expression is up-regulated in response to retinoic acid in both early Xenopus embryos and in human cell lines. Blocking retinoic acid signaling using a retinoic acid antagonist results in a corresponding decrease in the levels of ski mRNA. Finally, overexpression of SKI in human cells results in reduced levels of CYP26A1 mRNA, a known target of retinoic acid signaling.
  
  
  CONCLUSIONS
  Our results, coupled with the known ability of Ski to repress retinoic acid signaling, demonstrate that Ski expression is a novel negative feedback mechanism acting on retinoic acid signaling.
authors: Children's Health Research Institute, E. London, Ontario, Canada.
authors: Meaghan A
authors: MA
authors: Melling
authors: Charlotte R C
authors: CR
authors: Friendship
authors: Trevor G
authors: TG
authors: Shepherd
authors: Thomas A
authors: TA
authors: Drysdale
mesh_terms: D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000072516:Retinoic Acid 4-Hydroxylase; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D014981:Xenopus
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C060614:SKI protein, human; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D000072516:Retinoic Acid 4-Hydroxylase