GLI3 is processed to GLI3R by the proteasome

Stable Identifier
R-HSA-5610785
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Pathway
Species
Homo sapiens
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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
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Orthologous Events
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GlyCosmos
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