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Gene Review

GLI1  -  GLI family zinc finger 1

Homo sapiens

Synonyms: GLI, Glioma-associated oncogene, Oncogene GLI, Zinc finger protein GLI1
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Disease relevance of GLI1


High impact information on GLI1

  • In contrast, a group of distinct proteins, including FOXF1, POD1, GLI, and HOX family members, play important roles in the developing lung mesenchyme, from which pulmonary vessels and bronchial smooth muscle develop [6].
  • Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor [7].
  • Several of these mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling [8].
  • De-repression of SMOH culminates in the activation of one or more of the GLI transcription factors that regulate the transcription of downstream targets [8].
  • GLI gene and rhabdomyosarcoma [9].

Chemical compound and disease context of GLI1

  • The objective of this paper is to investigate the protein distribution of SHH and its receptor PTC, SMO and transcription factor GLI1 in various odontogenic tumors [10].
  • In pregnancy, the gut GLI response to glucose was reduced in the overweight gestational diabetics and abolished in the normal women [11].

Biological context of GLI1

  • In addition, pathway blockade in three metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to inhibition of cell proliferation, suggesting cell-autonomous pathway activation at different levels and showing an essential role for GLI1 in human cells [1].
  • In normal sebaceous glands IHH is expressed in differentiated sebocytes and the transcription factor GLI1 is activated in sebocyte progenitors, suggesting a paracrine signaling mechanism [12].
  • The zinc finger transcription factors GLI1 and GLI2 are considered mediators of the HH signal in epidermal cells, although their tumorigenic nature and their relative contribution to tumorigenesis are only poorly understood [13].
  • Interestingly, the phenotype of K5-Gli2DeltaN2 mice was strikingly similar to that reported after K5 promoter-driven overexpression of GLI1, which lacks an NH(2)-terminal region homologous to the Gli2 repressor domain [14].
  • Using the in vivo tadpole assay system, we further show that misexpression of GLI1 induces CNS hyperproliferation that depends on the activation of endogenous Gli1 function [15].

Anatomical context of GLI1


Associations of GLI1 with chemical compounds

  • Tryptophan residues at position 5 in each finger provide numerous non-helical inter-finger contacts reminiscent of those observed in GLI1 zinc fingers 1 and 2 [18].
  • SHH, PTC, SMO and GLI1 were detected more in the cytoplasm of the epithelial cells than in stromal cells [10].
  • The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE [19].
  • We next show that co-expression of Fu with transcription factors Gli1 and Gli2 significantly increases their protein levels and luciferase reporter activities, which are blocked by GA [20].
  • METHODS: Gli1 transcript levels were measured by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed, paraffin-embedded tissues of 68 cases of various skin tumors [21].

Physical interactions of GLI1

  • Using band shift and luciferase reporter assays, we now show that GLI2 binds the GLI-binding consensus sequence in the GLI1 promoter [22].
  • Twist activates GLI1 reporter expression through E-box +482 but requires binding of USF proteins to E-box +157 [5].
  • Detailed promoter analysis and gel shift assays identified three GLI binding sites in the human BCL2 cis-regulatory region [13].
  • HAN11 binds mDia1 and controls GLI1 transcriptional activity [23].
  • Furthermore, when produced in vitro, the GLI3 protein bound specifically to genomic DNA fragments containing GLI-binding sites [24].

Regulatory relationships of GLI1

  • GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter [22].
  • Apparently FU did not have any effect on SUFU induced inhibition of GLI [25].
  • While exogenous GLI1 increased the luciferase activity, exogenous beta-catenin also enhanced the activity under overexpression of GLI1 [26].
  • Additionally, deletion mapping of PTCH1 has revealed that the domains encompassed by amino acids 180-786 and 1058-1210 are of highest significance in inhibiting GLI1 gene activation [27].
  • This long FU and a much shorter isoform were compared for the ability to regulate GLI1 and GLI2 [25].

Other interactions of GLI1

  • In normal embryonic kidney tissue, GLI1 and/or GLI2 were bound to each target gene [28].
  • By contrast, treatment of embryonic kidney explants with cyclopamine decreased GLI1 and/or GLI2 binding, and induced binding of GLI3 [28].
  • Moreover, we have found that a C-terminal 19-amino acid deletion in SUFU (delta465) is sufficient to abrogate interaction with GLI1 [29].
  • Sonic hedgehog (Shh) binds to its receptor patched (PTCH), leading to the activation and repression of target genes via the GLI family of zinc-finger transcription factors [22].
  • The kinetics of FOXE1 induction are similar to the known direct target PTCH, and a 2.5 kb upstream fragment containing five GLI-binding sites activates transcription in a reporter assay [30].

Analytical, diagnostic and therapeutic context of GLI1


  1. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Sanchez, P., Hernández, A.M., Stecca, B., Kahler, A.J., DeGueme, A.M., Barrett, A., Beyna, M., Datta, M.W., Datta, S., Ruiz i Altaba, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Human GLI2 and GLI1 are part of a positive feedback mechanism in Basal Cell Carcinoma. Regl, G., Neill, G.W., Eichberger, T., Kasper, M., Ikram, M.S., Koller, J., Hintner, H., Quinn, A.G., Frischauf, A.M., Aberger, F. Oncogene (2002) [Pubmed]
  3. Dysregulation of hedgehog signalling predisposes to synovial chondromatosis. Hopyan, S., Nadesan, P., Yu, C., Wunder, J., Alman, B.A. J. Pathol. (2005) [Pubmed]
  4. Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. Tostar, U., Malm, C.J., Meis-Kindblom, J.M., Kindblom, L.G., Toftgård, R., Undén, A.B. J. Pathol. (2006) [Pubmed]
  5. Cooperative E-box regulation of human GLI1 by TWIST and USF. Villavicencio, E.H., Yoon, J.W., Frank, D.J., Füchtbauer, E.M., Walterhouse, D.O., Iannaccone, P.M. Genesis (2002) [Pubmed]
  6. Transcriptional control of lung morphogenesis. Maeda, Y., Davé, V., Whitsett, J.A. Physiol. Rev. (2007) [Pubmed]
  7. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Senée, V., Chelala, C., Duchatelet, S., Feng, D., Blanc, H., Cossec, J.C., Charon, C., Nicolino, M., Boileau, P., Cavener, D.R., Bougnères, P., Taha, D., Julier, C. Nat. Genet. (2006) [Pubmed]
  8. Mutations in SUFU predispose to medulloblastoma. Taylor, M.D., Liu, L., Raffel, C., Hui, C.C., Mainprize, T.G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A.M., Stavrou, T., Scherer, S.W., Dura, W.T., Wainwright, B., Squire, J.A., Rutka, J.T., Hogg, D. Nat. Genet. (2002) [Pubmed]
  9. GLI gene and rhabdomyosarcoma. Myklebost, O. Nat. Med. (1998) [Pubmed]
  10. Epithelial expression of SHH signaling pathway in odontogenic tumors. Zhang, L., Chen, X.M., Sun, Z.J., Bian, Z., Fan, M.W., Chen, Z. Oral Oncol. (2006) [Pubmed]
  11. Gastrointestinal insulinotropic hormones in normal and gestational-diabetic pregnancy: response to oral glucose. Hornnes, P.J., Kühl, C., Lauritsen, K.B. Diabetes (1981) [Pubmed]
  12. Indian hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis. Niemann, C., Unden, A.B., Lyle, S., Zouboulis, C.h.C., Toftgård, R., Watt, F.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  13. Activation of the BCL2 promoter in response to Hedgehog/GLI signal transduction is predominantly mediated by GLI2. Regl, G., Kasper, M., Schnidar, H., Eichberger, T., Neill, G.W., Philpott, M.P., Esterbauer, H., Hauser-Kronberger, C., Frischauf, A.M., Aberger, F. Cancer Res. (2004) [Pubmed]
  14. Dissecting the oncogenic potential of Gli2: deletion of an NH(2)-terminal fragment alters skin tumor phenotype. Sheng, H., Goich, S., Wang, A., Grachtchouk, M., Lowe, L., Mo, R., Lin, K., de Sauvage, F.J., Sasaki, H., Hui, C.C., Dlugosz, A.A. Cancer Res. (2002) [Pubmed]
  15. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Dahmane, N., Sánchez, P., Gitton, Y., Palma, V., Sun, T., Beyna, M., Weiner, H., Ruiz i Altaba, A. Development (2001) [Pubmed]
  16. Hedgehog signaling and response to cyclopamine differ in epithelial and stromal cells in benign breast and breast cancer. Mukherjee, S., Frolova, N., Sadlonova, A., Novak, Z., Steg, A., Page, G.P., Welch, D.R., Lobo-Ruppert, S.M., Ruppert, J.M., Johnson, M.R., Frost, A.R. Cancer Biol. Ther. (2006) [Pubmed]
  17. GLI1 localization in the germinal epithelial cells alternates between cytoplasm and nucleus: upregulation in transgenic mice blocks spermatogenesis in pachytene. Kroft, T.L., Patterson, J., Won Yoon, J., Doglio, L., Walterhouse, D.O., Iannaccone, P.M., Goldberg, E. Biol. Reprod. (2001) [Pubmed]
  18. Solution structure of a Zap1 zinc-responsive domain provides insights into metalloregulatory transcriptional repression in Saccharomyces cerevisiae. Wang, Z., Feng, L.S., Matskevich, V., Venkataraman, K., Parasuram, P., Laity, J.H. J. Mol. Biol. (2006) [Pubmed]
  19. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats. Katayama, S., Ashizawa, K., Gohma, H., Fukuhara, T., Narumi, K., Tsuzuki, Y., Tatemoto, H., Nakada, T., Nagai, K. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  20. Fused kinase is stabilized by Cdc37/Hsp90 and enhances Gli protein levels. Kise, Y., Takenaka, K., Tezuka, T., Yamamoto, T., Miki, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Molecular diagnosis of basal cell carcinoma and other basaloid cell neoplasms of the skin by the quantification of Gli1 transcript levels. Hatta, N., Hirano, T., Kimura, T., Hashimoto, K., Mehregan, D.R., Ansai, S., Takehara, K., Takata, M. J. Cutan. Pathol. (2005) [Pubmed]
  22. GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter. Ikram, M.S., Neill, G.W., Regl, G., Eichberger, T., Frischauf, A.M., Aberger, F., Quinn, A., Philpott, M. J. Invest. Dermatol. (2004) [Pubmed]
  23. HAN11 binds mDia1 and controls GLI1 transcriptional activity. Morita, K., Celso, C.L., Spencer-Dene, B., Zouboulis, C.C., Watt, F.M. J. Dermatol. Sci. (2006) [Pubmed]
  24. GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity. Ruppert, J.M., Vogelstein, B., Arheden, K., Kinzler, K.W. Mol. Cell. Biol. (1990) [Pubmed]
  25. The FU gene and its possible protein isoforms. Østerlund, T., Everman, D.B., Betz, R.C., Mosca, M., Nöthen, M.M., Schwartz, C.E., Zaphiropoulos, P.G., Toftgård, R. BMC Genomics (2004) [Pubmed]
  26. Enhancement of GLI1-transcriptional activity by beta-catenin in human cancer cells. Maeda, O., Kondo, M., Fujita, T., Usami, N., Fukui, T., Shimokata, K., Ando, T., Goto, H., Sekido, Y. Oncol. Rep. (2006) [Pubmed]
  27. Inhibition of GLI1 gene activation by Patched1. Rahnama, F., Shimokawa, T., Lauth, M., Finta, C., Kogerman, P., Teglund, S., Toftgård, R., Zaphiropoulos, P.G. Biochem. J. (2006) [Pubmed]
  28. GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Hu, M.C., Mo, R., Bhella, S., Wilson, C.W., Chuang, P.T., Hui, C.C., Rosenblum, N.D. Development (2006) [Pubmed]
  29. Characterization of the physical interaction of Gli proteins with SUFU proteins. Dunaeva, M., Michelson, P., Kogerman, P., Toftgard, R. J. Biol. Chem. (2003) [Pubmed]
  30. FOXE1, a new transcriptional target of GLI2 is expressed in human epidermis and basal cell carcinoma. Eichberger, T., Regl, G., Ikram, M.S., Neill, G.W., Philpott, M.P., Aberger, F., Frischauf, A.M. J. Invest. Dermatol. (2004) [Pubmed]
  31. Selective modulation of Hedgehog/GLI target gene expression by epidermal growth factor signaling in human keratinocytes. Kasper, M., Schnidar, H., Neill, G.W., Hanneder, M., Klingler, S., Blaas, L., Schmid, C., Hauser-Kronberger, C., Regl, G., Philpott, M.P., Aberger, F. Mol. Cell. Biol. (2006) [Pubmed]
  32. Sonic and desert hedgehog signaling in human fetal prostate development. Zhu, G., Zhau, H.E., He, H., Zhang, L., Shehata, B., Wang, X., Cerwinka, W.H., Elmore, J., He, D. Prostate (2007) [Pubmed]
  33. Hedgehog signaling in small-cell lung cancer: frequent in vivo but a rare event in vitro. Vestergaard, J., Pedersen, M.W., Pedersen, N., Ensinger, C., Tümer, Z., Tommerup, N., Poulsen, H.S., Larsen, L.A. Lung Cancer (2006) [Pubmed]
  34. Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. Yoon, J.W., Kita, Y., Frank, D.J., Majewski, R.R., Konicek, B.A., Nobrega, M.A., Jacob, H., Walterhouse, D., Iannaccone, P. J. Biol. Chem. (2002) [Pubmed]
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