Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Genes Dev
2006 Feb 01;203:276-81. doi: 10.1101/gad.1380906.
Show Gene links
Show Anatomy links
Dual degradation signals control Gli protein stability and tumor formation.
Huntzicker EG, Estay IS, Zhen H, Lokteva LA, Jackson PK, Oro AE.
???displayArticle.abstract???
Regulated protein destruction controls many key cellular processes with aberrant regulation increasingly found during carcinogenesis. Gli proteins mediate the transcriptional effects of the Sonic hedgehog pathway, which is implicated in up to 25% of human tumors. Here we show that Gli is rapidly destroyed by the proteasome and that mouse basal cell carcinoma induction correlates with Gli protein accumulation. We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals. These data argue that control of Gli protein accumulation underlies tumorigenesis and suggest a new avenue for antitumor therapy.
???displayArticle.pubmedLink???
16421275 ???displayArticle.pmcLink???PMC1361699 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Amit,
Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.
2002, Pubmed
Amit,
Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.
2002,
Pubmed Callahan,
MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription.
2004,
Pubmed Callahan,
Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through Sonic hedgehog signaling.
2001,
Pubmed Cheng,
Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex.
2002,
Pubmed Dai,
Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3.
1999,
Pubmed
,
Xenbase Dai,
A hedgehog-responsive region in the Drosophila wing disc is defined by debra-mediated ubiquitination and lysosomal degradation of Ci.
2003,
Pubmed Ding,
Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1.
1999,
Pubmed Grachtchouk,
The magnitude of hedgehog signaling activity defines skin tumor phenotype.
2003,
Pubmed Hutchin,
Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle.
2005,
Pubmed Jia,
Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I.
2004,
Pubmed Jiang,
Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb.
1998,
Pubmed Kinzler,
The GLI gene is a member of the Kruppel family of zinc finger proteins.
1988,
Pubmed
,
Xenbase Kogerman,
Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1.
1999,
Pubmed Lum,
The Hedgehog response network: sensors, switches, and routers.
2004,
Pubmed Margottin-Goguet,
Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.
2003,
Pubmed
,
Xenbase Méthot,
An absolute requirement for Cubitus interruptus in Hedgehog signaling.
2001,
Pubmed Mill,
Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development.
2003,
Pubmed Moshe,
Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome.
2004,
Pubmed
,
Xenbase Nilsson,
Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1.
2000,
Pubmed Oro,
Hair cycle regulation of Hedgehog signal reception.
2003,
Pubmed Oro,
Basal cell carcinomas in mice overexpressing sonic hedgehog.
1997,
Pubmed Pickart,
Back to the future with ubiquitin.
2004,
Pubmed Ramírez,
Sequences 5' of the bovine keratin 5 gene direct tissue- and cell-type-specific expression of a lacZ gene in the adult and during development.
1994,
Pubmed Reimann,
Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.
2001,
Pubmed
,
Xenbase Ruiz i Altaba,
Gli and hedgehog in cancer: tumours, embryos and stem cells.
2002,
Pubmed Sasaki,
Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling.
1999,
Pubmed
,
Xenbase Spencer,
Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP.
1999,
Pubmed Taipale,
Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.
2000,
Pubmed von Mering,
Distinct and regulated activities of human Gli proteins in Drosophila.
1999,
Pubmed
,
Xenbase Wang,
Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus.
1999,
Pubmed Wicking,
Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident.
1997,
Pubmed Winston,
The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.
1999,
Pubmed Yamasaki,
Cell cycle, proteolysis and cancer.
2004,
Pubmed Yoon,
GLI activates transcription through a herpes simplex viral protein 16-like activation domain.
1998,
Pubmed
