Expression of ski can act as a negative feedback mechanism on retinoic acid signaling

Authors

  • Meaghan A. Melling,

    1. Children's Health Research Institute, E. London, Ontario, Canada
    2. Department of Physiology and Pharmacology, University of Western Ontario, Canada
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  • Charlotte R.C. Friendship,

    1. Children's Health Research Institute, E. London, Ontario, Canada
    2. Department of Physiology and Pharmacology, University of Western Ontario, Canada
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  • Trevor G. Shepherd,

    1. Translational Ovarian Cancer Research Program, London Regional Cancer Program, Ontario, Canada
    2. Department of Anatomy and Cell Biology, University of Western Ontario, Canada
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  • Thomas A. Drysdale

    Corresponding author
    1. Children's Health Research Institute, E. London, Ontario, Canada
    2. Department of Physiology and Pharmacology, University of Western Ontario, Canada
    3. Department of Paediatrics, University of Western Ontario, Canada
    • Correspondence to: Thomas A. Drysdale, Children's Health Research Institute, 800 Commissioners Road, E. London, Ontario, N6C2V5 Canada. E-mail: tadrysda@uwo.ca

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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. Developmental Dynamics 242:604–613, 2013. © 2013 Wiley Periodicals, Inc.

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