Degradation of GLI1 by the proteasome

Stable Identifier
R-HSA-5610780
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
Summation

GLI1 is the most divergent of the 3 mammalian GLI transcription factors and lacks a transcriptional repressor domain. Although GLI1 is dispensible for development, the gene is an early transcriptional target of Hh signaling and the protein contributes a minor activation function in mammals (Dai et al, 1999; Bai et al, 2002; Park et al, 2000).
In the absence of Hh signaling, GLI1 is completely degraded by the proteasome, in contrast to the partial processing that occurs with GLI3. This differential response reflects the absence in GLI1 of two of the three elements identified in GLI3 that promote partial proteolysis; these are the zinc finger region, present in all GLI proteins, and an adjacent linker sequence and the degron, neither of which are found in the GLI1 protein (Schrader et al, 2011; Pan and Wang, 2007).

Literature References
PubMed ID Title Journal Year
10075717 Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3

Dai, P, Akimaru, H, Tanaka, Y, Maekawa, T, Nakafuku, M, Ishii, S

J. Biol. Chem. 1999
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
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
10725236 Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation

Park, HL, Bai, C, Platt, KA, Matise, MP, Beeghly, A, Hui, CC, Nakashima, M, Joyner, AL

Development 2000
12361967 Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway

Bai, CB, Auerbach, W, Lee, JS, Stephen, D, Joyner, AL

Development 2002
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