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Publication : Sufu recruits GSK3beta for efficient processing of Gli3.

First Author  Kise Y Year  2009
Journal  Biochem Biophys Res Commun Volume  387
Issue  3 Pages  569-74
PubMed ID  19622347 Mgi Jnum  J:152531
Mgi Id  MGI:4359096 Doi  10.1016/j.bbrc.2009.07.087
Citation  Kise Y, et al. (2009) Sufu recruits GSK3beta for efficient processing of Gli3. Biochem Biophys Res Commun 387(3):569-74
abstractText  Hedgehog (Hh) signaling activates the transcription factor Gli by suppressing the function of the suppressor of fused (Sufu) protein in mammals. Here, a novel role of mammalian Sufu is identified where it mediates the phosphorylation of Gli3 by GSK3beta, essential for Gli3 processing to generate a transcriptional repressor for Hh-target genes. Studies using Sufu(-/-) mouse embryonic fibroblasts and siRNA targeting Sufu demonstrate the requirement of Sufu for Gli3 processing. In addition, Sufu can bind to GSK3beta as well as Gli3, and mediates formation of the trimolecular complex Gli3/Sufu/GSK3beta. Thus, Sufu stimulates Gli3 phosphorylation by GSK3beta and Gli3 processing. Furthermore, Sonic Hh stimulation dissociates the Sufu/GSK3beta complex from Gli3, resulting in the blockade of Gli3 processing. Collectively, Sufu presumably functions as a GSK3beta recruiter for Hh-dependent regulation of Gli3 processing. Such a function is very similar to that of Costal2 in Drosophila, suggesting a functional complementation through evolution.
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