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XB-ART-46722
Dev Dyn June 1, 2013; 242 (6): 604-13.

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

Melling MA , Friendship CR , Shepherd TG , Drysdale TA .


Abstract
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. 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. 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.

PubMed ID: 23441061
Article link: Dev Dyn
Grant support: Canadian Institutes of Health Research

Genes referenced: ski actl6a cyp26a1 gapdh id3


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