Reactome | GLI3 is processed to GLI3R by the proteasome

GLI3 is processed to GLI3R by the proteasome

Stable Identifier

R-HSA-5610785

Type

Pathway

Species

Homo sapiens

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GLI3 is processed to GLI3R by the proteasome

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In the absence of Hh signaling, the majority of full-length GLI3 is partially processed by the proteasome to a shorter form that serves as the principal repressor of Hh target genes (Wang et al, 2000). Processing depends on phosphorylation at 6 sites by PKA, which primes the protein for subsequent phosphorylation at adjacent sites by CK1 and GSK3. The hyperphosphorylated protein is then a direct target for betaTrCP-dependent ubiquitination and proteasome-dependent processing (Wang and Li, 2006; Tempe et al, 2006; Wen et al, 2010; Schrader et al, 2011; Pan and Wang, 2007).

Literature References

PubMed ID	Title	Journal	Year
17283082	A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome Pan, Y, Wang, B	J. Biol. Chem.	2007
16705181	Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP Tempe, D, Casas, M, Karaz, S, Blanchet-Tournier, MF, Concordet, JP	Mol Cell Biol	2006
10693759	Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb Wang, B, Fallon, JF, Beachy, PA	Cell	2000
20154143	Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation Wen, X, Lai, CK, Evangelista, M, Hongo, JA, de Sauvage, FJ, Scales, SJ	Mol. Cell. Biol.	2010
21921029	A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome Schrader, EK, Harstad, KG, Holmgren, RA, Matouschek, A	J. Biol. Chem.	2011
16371461	Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing Wang, B, Li, Y	Proc. Natl. Acad. Sci. U.S.A.	2006