GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions

Kim, Yong Sik; Nakanishi, Gen; Lewandoski, Mark; Jetten, Anton M.

doi:10.1093/nar/gkg776

Cited by 110 publications

(160 citation statements)

References 70 publications

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“…The N-terminal Region of Glis3 Influences Glis3-mediated Transcriptional Regulation-Previous studies focused predominantly on two domains within Glis3: the centrally located ZFD, which mediates the recognition of GlisBS, and a transactivation domain (TAD) within the C terminus of Glis3 that is required for its transactivation function (1,4,9). We reported previously that Glis3 robustly activates transcription of murine Ins2 via its proximal promoter, which contains two functional Glis-responsive elements (7,8).…”

Section: Resultsmentioning

confidence: 99%

“…Homology among Glis, Zic, and Ci/Gli proteins is limited to the five Cys 2 -His 2 zinc finger motifs shared by all three subfamilies, with little or no similarity outside of the region (4). The zinc finger domain of Glis3 is required for the recognition of specific DNA-binding sites within the regulatory regions of target genes (4 -8).…”

mentioning

confidence: 99%

“…In vitro studies have shown that Glis3 optimally binds the consensus sequence 5Ј-(G/C)TGGGGGGT(A/C)-3Ј, designated as the GlisBS (9). In addition to its zinc finger domain (ZFD), the Glis3 C terminus has proven indispensable for transactivation, whereas little is known currently about the role of its N terminus (4,9).…”

mentioning

confidence: 99%

“…Previous studies have shown that the DNA-binding domain and transcriptional activation domain are localized in the center and within the C terminus of Glis3, respectively (1,4,9); however, little is known about the function of its 500-amino acid N terminus. The objective of this study was to examine the potential role of the N terminus in modulating Glis3 activity.…”

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confidence: 99%

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Modulation of the Transactivation Function and Stability of Krüppel-like Zinc Finger Protein Gli-similar 3 (Glis3) by Suppressor of Fused

ZeRuth

Yang

Jetten

2011

Journal of Biological Chemistry

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Glis3 is a member of the Glis subfamily of Krüppel-like zinc finger transcription factors. Recently, Glis3 has been linked to both type I and type II diabetes and shown to positively regulate insulin gene expression. In this study, we have identified a region within the N terminus of Glis3 that shares high levels of homology with the Cubitus interruptus (Ci)/Gli family of proteins. We demonstrated that Glis3 interacts with Suppressor of Fused (SUFU), which involves a VYGHF motif located within this conserved region. We further showed that SUFU is able to inhibit the activation of the insulin promoter by Glis3 but not the activation by a Glis3 mutant deficient in its ability to bind SUFU, suggesting that the inhibitory effect is dependent on the interaction between the two proteins. Exogenous SUFU did not affect the nuclear localization of Glis3; however, Glis3 promoted the nuclear accumulation of SUFU. Additionally, we demonstrated that SUFU stabilizes Glis3 in part by antagonizing the Glis3 association with a Cullin 3-based E3 ubiquitin ligase that promotes the ubiquitination and degradation of Glis3. This is the first reported instance of Glis3 interacting with SUFU and suggests a novel role for SUFU in the modulation of Glis3 signaling. Given the critical role of Glis3 in pancreatic ␤-cell generation and maintenance, the elevated Glis3 expression in several cancers, and the established role of SUFU as a tumor suppressor, these data provide further insight into Glis3 regulation and its function in development and disease.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Modulation of the Transactivation Function and Stability of Krüppel-like Zinc Finger Protein Gli-similar 3 (Glis3) by Suppressor of Fused

ZeRuth

Yang

Jetten

2011

Journal of Biological Chemistry

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“…GLIS3 is a member of the Krüppel-like zinc finger protein subfamily that was named due to its similarity to Drosophila regulatory protein Krüppel (Kim et al 2003). Mutations of GLIS3 cause a neonatal diabetes syndrome characterized by neonatal diabetes, congenital hypothyroidism and polycystic kidney (Senee et al 2006), which can be phenocopied in Glis3-deficient mice (Kang et al 2009b, Watanabe et al 2009.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes

Wen

Yang

2017

Journal of Molecular Endocrinology

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GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism and polycystic kidney.

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An emerging, recognizable facial phenotype in association with mutations in GLI‐similar 3 (GLIS3)

Dimitri

Franco

Habeb

et al. 2016

American J of Med Genetics Pt A

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Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non‐autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico‐medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI‐similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low‐set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc.

show abstract

GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions

Cited by 110 publications

References 70 publications

Modulation of the Transactivation Function and Stability of Krüppel-like Zinc Finger Protein Gli-similar 3 (Glis3) by Suppressor of Fused

Modulation of the Transactivation Function and Stability of Krüppel-like Zinc Finger Protein Gli-similar 3 (Glis3) by Suppressor of Fused

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes

An emerging, recognizable facial phenotype in association with mutations in GLI‐similar 3 (GLIS3)

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