title: Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease.
abstract: Gli-similar (Glis) 1-3 proteins constitute a subfamily of Krüppel-like zinc-finger proteins that are closely related to members of the Gli family. Glis proteins have been implicated in several pathologies, including cystic kidney disease, diabetes, hypothyroidism, fibrosis, osteoporosis, psoriasis, and cancer. In humans, a mutation in the Glis2 gene has been linked to the development of nephronophthisis (NPHP), a recessive cystic kidney disease, while mutations in Glis3 lead to an extended multisystem phenotype that includes the development of neonatal diabetes, polycystic kidneys, congenital hypothyroidism, and facial dysmorphism. Glis3 has also been identified as a risk locus for type-1 and type-2 diabetes and additional studies have revealed a role for Glis3 in pancreatic endocrine development, β-cell maintenance, and insulin regulation. Similar to Gli1-3, Glis2 and 3 have been reported to localize to the primary cilium. These studies appear to suggest that Glis proteins are part of a primary cilium-associated signaling pathway(s). It has been hypothesized that Glis proteins are activated through posttranslational modifications and subsequently translocate to the nucleus where they regulate transcription by interacting with Glis-binding sites in the promoter regions of target genes. This chapter summarizes the current state of knowledge regarding mechanisms of action of the Glis family of proteins, their physiological functions, as well as their roles in disease.
authors.affiliation: Cell Biology Section, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Lichti-Kaiser
authors.forename: Gary
authors.initials: G
authors.lastname: ZeRuth
authors.forename: Hong Soon
authors.initials: HS
authors.lastname: Kang
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Vasanth
authors.forename: Anton M
authors.initials: AM
authors.lastname: Jetten
mesh_terms: D001665:Binding Sites; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D000071676:Zinc Finger Protein GLI1; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
chemical_list: C400551:GLI1 protein, human; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1