Degradation of GLI2 by the proteasome

Stable Identifier
Homo sapiens
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The primary role of the GLI2 protein is as an activator of Hh-dependent signaling upon pathway stimulation; in the absence of Hh ligand, a small fraction of GLI2 appears to be processed to a repressor form, but the bulk of the protein is completely degraded by the proteasome (reviewed in Briscoe and Therond, 2013). Both the processing and the degradation of GLI2 is dependent upon sequential phosphorylation of multiple serine residues by PKA, CK1 and GSK3, analagous to the requirement for these kinases in the processing of GLI3 (Pan et al, 2009; Pan et al, 2006; Pan and Wang, 2007). The differential processing of GLI2 and GLI3 depends on the processing determinant domain (PDD) in the C-terminal of the proteins, which directs the partial proteolysis of GLI3 in the absence of Hh signal. Substitution of 2 amino-acids from GLI3 into the GLI2 protein is sufficient to promote efficient processing of GLI2 to the repressor form (Pan and Wang, 2007).

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