This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kinzler, K W
Right arrow Articles by Vogelstein, B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kinzler, K W
Right arrow Articles by Vogelstein, B

 Previous Article  |  Next Article 

Mol Cell Biol. 1990 February; 10(2): 634-642

The GLI gene encodes a nuclear protein which binds specific sequences in the human genome.

K W Kinzler and B Vogelstein

Johns Hopkins Oncology Center, Baltimore, Maryland 21231.

ABSTRACT

The GLI gene is amplified in a subset of human tumors and encodes a protein product with five zinc finger DNA-binding motifs. In this study, we show that the GLI gene product has a predominantly nuclear localization and binds DNA in a sequence-specific fashion. Three GLI binding sites were identified by using a novel procedure in which total human DNA was bound to a GLI recombinant fusion protein, and the polymerase chain reaction was used to amplify and recover the bound sequences. The GLI protein protected a 23- to 24-base region within all three binding sites, and the protected region in each case included the 9-base-pair sequence 5'-GACCACCCA-3'. One of the binding sites was contained within a 63-base-pair repeat of the variable number of tandem repeat type, whereas the other two sites were represented once in the genome. The approach used here to identify GLI binding sites should be applicable to the characterization of other zinc finger proteins.

Mol Cell Biol. 1990 February; 10(2): 634-642




This article has been cited by other articles:

  • Lo, H.-W., Zhu, H., Cao, X., Aldrich, A., Ali-Osman, F. (2009). A Novel Splice Variant of GLI1 That Promotes Glioblastoma Cell Migration and Invasion. Cancer Res. 69: 6790-6798 [Abstract] [Full Text]  
  • Das, S., Harris, L. G., Metge, B. J., Liu, S., Riker, A. I., Samant, R. S., Shevde, L. A. (2009). The Hedgehog Pathway Transcription Factor GLI1 Promotes Malignant Behavior of Cancer Cells by Up-regulating Osteopontin. J. Biol. Chem. 284: 22888-22897 [Abstract] [Full Text]  
  • Xie, J. (2009). Activation of Hedgehog Signaling in Human Cancer: Basic Mechanisms and Clinical Implications. aacredbook 2009: 25-41 [Full Text]  
  • Madison, B. B., McKenna, L. B., Dolson, D., Epstein, D. J., Kaestner, K. H. (2009). FoxF1 and FoxL1 Link Hedgehog Signaling and the Control of Epithelial Proliferation in the Developing Stomach and Intestine. J. Biol. Chem. 284: 5936-5944 [Abstract] [Full Text]  
  • Yu, M., Gipp, J., Yoon, J. W., Iannaccone, P., Walterhouse, D., Bushman, W. (2009). Sonic Hedgehog-responsive Genes in the Fetal Prostate. J. Biol. Chem. 284: 5620-5629 [Abstract] [Full Text]  
  • Liao, X., Siu, M. K.Y., Au, C. W.H., Wong, E. S.Y., Chan, H. Y., Ip, P. P.C., Ngan, H. Y.S., Cheung, A. N.Y. (2009). Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30: 131-140 [Abstract] [Full Text]  
  • Hatayama, M., Tomizawa, T., Sakai-Kato, K., Bouvagnet, P., Kose, S., Imamoto, N., Yokoyama, S., Utsunomiya-Tate, N., Mikoshiba, K., Kigawa, T., Aruga, J. (2008). Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain. Hum Mol Genet 17: 3459-3473 [Abstract] [Full Text]  
  • Vokes, S. A., Ji, H., Wong, W. H., McMahon, A. P. (2008). A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb. Genes Dev. 22: 2651-2663 [Abstract] [Full Text]  
  • Varjosalo, M., Taipale, J. (2008). Hedgehog: functions and mechanisms. Genes Dev. 22: 2454-2472 [Abstract] [Full Text]  
  • Eichberger, T., Kaser, A., Pixner, C., Schmid, C., Klingler, S., Winklmayr, M., Hauser-Kronberger, C., Aberger, F., Frischauf, A.-M. (2008). GLI2-specific Transcriptional Activation of the Bone Morphogenetic Protein/Activin Antagonist Follistatin in Human Epidermal Cells. J. Biol. Chem. 283: 12426-12437 [Abstract] [Full Text]  
  • Marsh, D., Dickinson, S., Neill, G. W., Marshall, J. F., Hart, I. R., Thomas, G. J. (2008). {alpha}v{beta}6 Integrin Promotes the Invasion of Morphoeic Basal Cell Carcinoma through Stromal Modulation. Cancer Res. 68: 3295-3303 [Abstract] [Full Text]  
  • Kim, Y.-S., Kang, H. S., Herbert, R., Beak, J. Y., Collins, J. B., Grissom, S. F., Jetten, A. M. (2008). Kruppel-Like Zinc Finger Protein Glis2 Is Essential for the Maintenance of Normal Renal Functions. Mol. Cell. Biol. 28: 2358-2367 [Abstract] [Full Text]  
  • Beak, J. Y., Kang, H. S., Kim, Y.-S., Jetten, A. M. (2008). Functional analysis of the zinc finger and activation domains of Glis3 and mutant Glis3(NDH1). Nucleic Acids Res 36: 1690-1702 [Abstract] [Full Text]  
  • Ajo-Franklin, C. M., Drubin, D. A., Eskin, J. A., Gee, E. P.S., Landgraf, D., Phillips, I., Silver, P. A. (2007). Rational design of memory in eukaryotic cells. Genes Dev. 21: 2271-2276 [Abstract] [Full Text]  
  • Bien-Willner, G. A., Stankiewicz, P., Lupski, J. R. (2007). SOX9cre1, a cis-acting regulatory element located 1.1 Mb upstream of SOX9, mediates its enhancement through the SHH pathway. Hum Mol Genet 16: 1143-1156 [Abstract] [Full Text]  
  • Vokes, S. A., Ji, H., McCuine, S., Tenzen, T., Giles, S., Zhong, S., Longabaugh, W. J. R., Davidson, E. H., Wong, W. H., McMahon, A. P. (2007). Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning. Development 134: 1977-1989 [Abstract] [Full Text]  
  • Ji, H., Vokes, S. A., Wong, W. H. (2006). A comparative analysis of genome-wide chromatin immunoprecipitation data for mammalian transcription factors. Nucleic Acids Res 34: e146-e146 [Abstract] [Full Text]  
  • He, J., Sheng, T., Stelter, A. A., Li, C., Zhang, X., Sinha, M., Luxon, B. A., Xie, J. (2006). Suppressing Wnt Signaling by the Hedgehog Pathway through sFRP-1. J. Biol. Chem. 281: 35598-35602 [Abstract] [Full Text]  
  • Xu, J., Srinivas, B. P., Tay, S. Y., Mak, A., Yu, X., Lee, S. G. P., Yang, H., Govindarajan, K. R., Leong, B., Bourque, G., Mathavan, S., Roy, S. (2006). Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development. Genetics 174: 735-752 [Abstract] [Full Text]  
  • Bird, A. J., Swierczek, S., Qiao, W., Eide, D. J., Winge, D. R. (2006). Zinc Metalloregulation of the Zinc Finger Pair Domain. J. Biol. Chem. 281: 25326-25335 [Abstract] [Full Text]  
  • 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. (2006). Selective Modulation of Hedgehog/GLI Target Gene Expression by Epidermal Growth Factor Signaling in Human Keratinocytes.. Mol. Cell. Biol. 26: 6283-6298 [Abstract] [Full Text]  
  • Dasari, V., Gallup, M., Lemjabbar, H., Maltseva, I., McNamara, N. (2006). Epithelial-Mesenchymal Transition in Lung Cancer: Is Tobacco the "Smoking Gun"?. Am. J. Respir. Cell Mol. Bio. 35: 3-9 [Full Text]  
  • Pan, Y., Bai, C. B., Joyner, A. L., Wang, B. (2006). Sonic hedgehog Signaling Regulates Gli2 Transcriptional Activity by Suppressing Its Processing and Degradation.. Mol. Cell. Biol. 26: 3365-3377 [Abstract] [Full Text]  
  • Hu, M. C., Mo, R., Bhella, S., Wilson, C. W., Chuang, P.-T., Hui, C.-c., Rosenblum, N. D. (2006). GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Development 133: 569-578 [Abstract] [Full Text]  
  • Sheng, T., Chi, S., Zhang, X., Xie, J. (2006). Regulation of Gli1 Localization by the cAMP/Protein Kinase A Signaling Axis through a Site Near the Nuclear Localization Signal. J. Biol. Chem. 281: 9-12 [Abstract] [Full Text]  
  • Wang, B., Li, Y. (2006). Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing. Proc. Natl. Acad. Sci. USA 103: 33-38 [Abstract] [Full Text]  
  • Regl, G., Kasper, M., Schnidar, H., Eichberger, T., Neill, G. W., Philpott, M. P., Esterbauer, H., Hauser-Kronberger, C., Frischauf, A.-M., Aberger, F. (2004). Activation of the BCL2 Promoter in Response to Hedgehog/GLI Signal Transduction Is Predominantly Mediated by GLI2. Cancer Res. 64: 7724-7731 [Abstract] [Full Text]  
  • Brancaccio, A., Minichiello, A., Grachtchouk, M., Antonini, D., Sheng, H., Parlato, R., Dathan, N., Dlugosz, A. A., Missero, C. (2004). Requirement of the forkhead gene Foxe1, a target of sonic hedgehog signaling, in hair follicle morphogenesis. Hum Mol Genet 13: 2595-2606 [Abstract] [Full Text]  
  • Ganss, B., Jheon, A. (2004). ZINC FINGER TRANSCRIPTION FACTORS IN SKELETAL DEVELOPMENT. CROBM 15: 282-297 [Abstract] [Full Text]  
  • Cui, C., Elsam, T., Tian, Q., Seykora, J. T., Grachtchouk, M., Dlugosz, A., Tseng, H. (2004). Gli Proteins Up-Regulate the Expression of Basonuclin in Basal Cell Carcinoma. Cancer Res. 64: 5651-5658 [Abstract] [Full Text]  
  • Ding, Z., Gillespie, L. L., Mercer, F. C., Paterno, G. D. (2004). The SANT Domain of Human MI-ER1 Interacts with Sp1 to Interfere with GC Box Recognition and Repress Transcription from Its Own Promoter. J. Biol. Chem. 279: 28009-28016 [Abstract] [Full Text]  
  • Dahlen, A., Fletcher, C. D. M., Mertens, F., Fletcher, J. A., Perez-Atayde, A. R., Hicks, M. J., Debiec-Rychter, M., Sciot, R., Wejde, J., Wedin, R., Mandahl, N., Panagopoulos, I. (2004). Activation of the GLI Oncogene through Fusion with the {beta}-Actin Gene (ACTB) in a Group of Distinctive Pericytic Neoplasms: Pericytoma with t(7;12). Am. J. Pathol. 164: 1645-1653 [Abstract] [Full Text]  
  • Bigelow, R. L. H., Chari, N. S., Unden, A. B., Spurgers, K. B., Lee, S., Roop, D. R., Toftgard, R., McDonnell, T. J. (2004). Transcriptional Regulation of bcl-2 Mediated by the Sonic Hedgehog Signaling Pathway through gli-1. J. Biol. Chem. 279: 1197-1205 [Abstract] [Full Text]  
  • Lunde, K., Trimble, J. L., Guichard, A., Guss, K. A., Nauber, U., Bier, E. (2003). Activation of the knirps locus links patterning to morphogenesis of the second wing vein in Drosophila. Development 130: 235-248 [Abstract] [Full Text]  
  • Louro, I. D., Bailey, E. C., Li, X., South, L. S., McKie-Bell, P. R., Yoder, B. K., Huang, C. C., Johnson, M. R., Hill, A. E., Johnson, R. L., Ruppert, J. M. (2002). Comparative Gene Expression Profile Analysis of GLI and c-MYC in an Epithelial Model of Malignant Transformation. Cancer Res. 62: 5867-5873 [Abstract] [Full Text]  
  • Kim, Y.-S., Lewandoski, M., Perantoni, A. O., Kurebayashi, S., Nakanishi, G., Jetten, A. M. (2002). Identification of Glis1, a Novel Gli-related, Kruppel-like Zinc Finger Protein Containing Transactivation and Repressor Functions. J. Biol. Chem. 277: 30901-30913 [Abstract] [Full Text]  
  • Teh, M.-T., Wong, S.-T., Neill, G. W., Ghali, L. R., Philpott, M. P., Quinn, A. G. (2002). FOXM1 Is a Downstream Target of Gli1 in Basal Cell Carcinomas. Cancer Res. 62: 4773-4780 [Abstract] [Full Text]  
  • Solecki, D. J., Gromeier, M., Mueller, S., Bernhardt, G., Wimmer, E. (2002). Expression of the Human Poliovirus Receptor/CD155 Gene Is Activated by Sonic Hedgehog. J. Biol. Chem. 277: 25697-25702 [Abstract] [Full Text]  
  • Cheng, S. Y., Bishop, J. M. (2002). Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex. Proc. Natl. Acad. Sci. USA 99: 5442-5447 [Abstract] [Full Text]  
  • Zhang, F., Nakanishi, G., Kurebayashi, S., Yoshino, K., Perantoni, A., Kim, Y.-S., Jetten, A. M. (2002). Characterization of Glis2, a Novel Gene Encoding a Gli-related, Kruppel-like Transcription Factor with Transactivation and Repressor Functions. ROLES IN KIDNEY DEVELOPMENT AND NEUROGENESIS. J. Biol. Chem. 277: 10139-10149 [Abstract] [Full Text]  
  • Gustafsson, M. K., Pan, H., Pinney, D. F., Liu, Y., Lewandowski, A., Epstein, D. J., Emerson, C. P. Jr. (2002). Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. Genes Dev. 16: 114-126 [Abstract] [Full Text]  
  • Lamar, E, Kintner, C, Goulding, M (2001). Identification of NKL, a novel Gli-Kruppel zinc-finger protein that promotes neuronal differentiation. Development 128: 1335-1346 [Abstract]  
  • Chen, Y., Goodman, R. H., Smolik, S. M. (2000). Cubitus interruptus Requires Drosophila CREB-Binding Protein To Activate wingless Expression in the Drosophila Embryo. Mol. Cell. Biol. 20: 1616-1625 [Abstract] [Full Text]  
  • Muller, B, Basler, K (2000). The repressor and activator forms of Cubitus interruptus control Hedgehog target genes through common generic gli-binding sites. Development 127: 2999-3007 [Abstract]  
  • Park, H., Bai, C, Platt, K., Matise, M., Beeghly, A, Hui, C., Nakashima, M, Joyner, A. (2000). Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development 127: 1593-1605 [Abstract]  
  • Dan, S., Tanimura, A., Yoshida, M. (1999). Interaction of Gli2 with CREB Protein on DNA Elements in the Long Terminal Repeat of Human T-Cell Leukemia Virus Type 1 Is Responsible for Transcriptional Activation by Tax Protein. J. Virol. 73: 3258-3263 [Abstract] [Full Text]  
  • Stein, U., Eder, C., Karsten, U., Haensch, W., Walther, W., Schlag, P. M. (1999). GLI Gene Expression in Bone and Soft Tissue Sarcomas of Adult Patients Correlates with Tumor Grade. Cancer Res. 59: 1890-1895 [Abstract] [Full Text]  
  • Dai, P., Akimaru, H., Tanaka, Y., Maekawa, T., Nakafuku, M., Ishii, S. (1999). Sonic Hedgehog-induced Activation of the Gli1 Promoter Is Mediated by GLI3. J. Biol. Chem. 274: 8143-8152 [Abstract] [Full Text]  
  • Hepker, J, Blackman, R., Holmgren, R (1999). Cubitus interruptus is necessary but not sufficient for direct activation of a wing-specific decapentaplegic enhancer. Development 126: 3669-3677 [Abstract]  
  • Muller, F, Chang, B, Albert, S, Fischer, N, Tora, L, Strahle, U (1999). Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord. Development 126: 2103-2116 [Abstract]  
  • Tanimura, A., Dan, S., Yoshida, M. (1998). Cloning of Novel Isoforms of the Human Gli2 Oncogene and Their Activities To Enhance Tax-Dependent Transcription of the Human T-Cell Leukemia Virus Type 1 Genome. J. Virol. 72: 3958-3964 [Abstract] [Full Text]  
  • Yoon, J. W., Liu, C. Z., Yang, J. T., Swart, R., Iannaccone, P., Walterhouse, D. (1998). GLI Activates Transcription through a Herpes Simplex Viral Protein 16-Like Activation Domain. J. Biol. Chem. 273: 3496-3501 [Abstract] [Full Text]  
  • Ruiz i Altaba, A (1998). Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development 125: 2203-2212 [Abstract]  
  • Tanaka, Y., Naruse, I., Maekawa, T., Masuya, H., Shiroishi, T., Ishii, S. (1997). Abnormal skeletal patterning in embryos lacking a single Cbp allele: A partial similarity with Rubinstein-Taybi syndrome. Proc. Natl. Acad. Sci. USA 94: 10215-10220 [Abstract] [Full Text]  
  • Von Ohlen, T., Lessing, D., Nusse, R., Hooper, J. E. (1997). Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein. Proc. Natl. Acad. Sci. USA 94: 2404-2409 [Abstract] [Full Text]  
  • Lee, J, Platt, K., Censullo, P, Ruiz i Altaba, A (1997). Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development 124: 2537-2552 [Abstract]  
  • Sasaki, H, Hui, C, Nakafuku, M, Kondoh, H (1997). A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development 124: 1313-1322 [Abstract]  
  • Hepker, J, Wang, Q., Motzny, C., Holmgren, R, Orenic, T. (1997). Drosophila cubitus interruptus forms a negative feedback loop with patched and regulates expression of Hedgehog target genes. Development 124: 549-558 [Abstract]  
  • Alexandre, C, Jacinto, A, Ingham, P W (1996). Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins.. Genes Dev. 10: 2003-2013 [Abstract]  
  • Mortlock, D P, Nelson, M R, Innis, J W (1996). An efficient method for isolating putative promoters and 5'-transcribed sequences from large genomic clones.. Genome Res 6: 327-335 [Abstract]  
  • Kang, S.-H., Brown, D. A., Kitajima, I., Xu, X., Heidenreich, O., Gryaznov, S., Nerenberg, M. (1996). Binding and Functional Effects of Transcriptional Factor Sp1 on the Murine Interleukin-6 Promotor. J. Biol. Chem. 271: 7330-7335 [Abstract] [Full Text]  
  • Goodrich, L V, Johnson, R L, Milenkovic, L, McMahon, J A, Scott, M P (1996). Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog.. Genes Dev. 10: 301-312 [Abstract]  
  • de Bono, M, Zarkower, D, Hodgkin, J (1995). Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1.. Genes Dev. 9: 155-167 [Abstract]  
  • Pavletich, N., Pabo, C. (1993). Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science 261: 1701-1707 [Abstract]  
  • Tabata, T, Eaton, S, Kornberg, T B (1992). The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation.. Genes Dev. 6: 2635-2645 [Abstract]  
  • Bickmore, W., Oghene, K, Little, M., Seawright, A, van Heyningen, V, Hastie, N. (1992). Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript. Science 257: 235-237 [Abstract]  
  • Wilson, T., Fahrner, T., Johnston, M, Milbrandt, J (1991). Identification of the DNA binding site for NGFI-B by genetic selection in yeast. Science 252: 1296-1300 [Abstract]  
  • Chittenden, T., Livingston, D.M., Kaelin, W.G. Jr. (1991). RB Associates with an E2F-like, Sequence-specific DNA-binding Protein. Cold Spring Harb Symp Quant Biol 56: 187-195 [Abstract]  
  • Orenic, T V, Slusarski, D C, Kroll, K L, Holmgren, R A (1990). Cloning and characterization of the segment polarity gene cubitus interruptus Dominant of Drosophila.. Genes Dev. 4: 1053-1067 [Abstract]  
  • Koyabu, Y., Nakata, K., Mizugishi, K., Aruga, J., Mikoshiba, K. (2001). Physical and Functional Interactions between Zic and Gli Proteins. J. Biol. Chem. 276: 6889-6892 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»