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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2012 June 8; 287(24): 20490.
PMCID: PMC3370233

How SUMO Controls the Activity of the Major Transcription Factor GLI2♦

Small Ubiquitin-like Modifier (SUMO) Modification Inhibits GLI2 Protein Transcriptional Activity in Vitro and in Vivo

♦ See referenced article, J. Biol. Chem. 2012, 287, 20483–20489

A transcription factor called GLI2 is the major activator of the Hedgehog signaling pathway, which orients an embryo from head to tail (or toe) and side to side. However, the details of how GLI2 activity is regulated are not clear. In this Paper of the Week, a team led by Baolin Wang at the Weill Medical College of Cornell University in New York demonstrated using in vitro and, more importantly, in vivo systems that GLI2 transcriptional activity was inhibited by SUMO modification at two lysine residues. GLI2 SUMO modification was regulated by protein kinase A phosphorylation as well as Hedgehog signaling. The investigators demonstrated that SUMO modification prevented GLI2 from binding to the lysine deacetylase HDAC5. Wang and colleagues concluded, “Taken together, our results suggest that SUMO modification inhibits GLI2 transcriptional activity by recruiting HDAC5.”

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A GLI2 mutant resistant to SUMO modification is more active than wild type GLI2 in mouse embryos.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology