title: Gli proteins in development and disease.
abstract: Gli zinc-finger proteins are transcription factors involved in the intracellular signal transduction controlled by the Hedgehog family of secreted molecules. They are frequently mutated in human congenital malformations, and their abnormal regulation leads to tumorigenesis. Genetic studies in several model systems indicate that their activity is tightly regulated by Hedgehog signaling through various posttranslational modifications, including phosphorylation, ubiquitin-mediated degradation, and proteolytic processing, as well as through nucleocytoplasmic shuttling. In vertebrate cells, primary cilia are required for the sensing of Hedgehog pathway activity and involved in the processing and activation of Gli proteins. Two evolutionarily conserved Hedgehog pathway components, Suppressor of fused and Kif7, are core intracellular regulators of mammalian Gli proteins. Recent studies revealed that Gli proteins are also regulated transcriptionally and posttranslationally through noncanonical mechanisms independent of Hedgehog signaling. In this review, we describe the regulation of Gli proteins during development and discuss possible mechanisms for their abnormal activation during tumorigenesis.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. cchui@sickkids.ca
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
authors.forename: Stephane
authors.initials: S
authors.lastname: Angers
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D000013:Congenital Abnormalities; D005121:Extremities / Q000033:anatomy & histology / Q000254:growth & development; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D054259:Neural Tube / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1; D016335:Zinc Fingers
chemical_list: D002843:Chromatin; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C502069:KIF7 protein, human; D015513:Oncogene Proteins; D012097:Repressor Proteins; C490764:SUFU protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D046988:Proteasome Endopeptidase Complex; D016547:Kinesins