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

ReviewStatus

5/5

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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
16705181	Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP Tempe, D, Concordet, JP, Casas, M, Blanchet-Tournier, MF, Karaz, S	Mol Cell Biol	2006
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
10693759	Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb Fallon, JF, Beachy, PA, Wang, B	Cell	2000
20154143	Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation Scales, SJ, Hongo, JA, Wen, X, Evangelista, M, Lai, CK, de Sauvage, FJ	Mol. Cell. Biol.	2010
21921029	A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome Matouschek, A, Holmgren, RA, Schrader, EK, Harstad, KG	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