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GLI2  -  GLI family zinc finger 2

Homo sapiens

Synonyms: CJS, GLI family zinc finger protein 2, HPE9, PHS2, THP, ...
 
 
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Disease relevance of GLI2

 

High impact information on GLI2

  • Furthermore, we localize Hh function to a stage preceding pre-T cell receptor signaling, connect Smo signaling to the activity of the Gli1 and Gli2 transcription factors and demonstrate that Hh affects regulators of thymocyte survival and proliferation [7].
  • Here we show that THP (allopregnanolone), a steroid that is released as a result of stress, increases anxiety in pubertal female mice, in contrast to its anxiety-reducing effect in adults [8].
  • Although this inhibition is increased by THP administration before puberty and in adults, during puberty THP reduces the tonic inhibition of pyramidal cells in hippocampal region CA1, leading to increased excitability [8].
  • THP also decreases the outward current at recombinant alpha4beta2delta receptors, and this effect depends on arginine 353 in the alpha4 subunit, a putative site for modulation by Cl(-) [8].
  • Protein kinase A (PKA) and glycogen synthase kinase 3beta sequentially phosphorylate Gli2 at multiple sites, identified by mutagenesis, thus resulting in a reduction of its transcriptional activity [9].
 

Chemical compound and disease context of GLI2

 

Biological context of GLI2

 

Anatomical context of GLI2

  • The data suggest a role for GLI2 in Hh-induced epidermal neoplasia by opposing epithelial cell cycle arrest signals and epidermal differentiation [11].
  • Finally, using in situ hybridization, we show that GLI2 is expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal skin as well as in BCC tumor islands [12].
  • Here, we show that loss-of-function mutations in the human GLI2 gene are associated with a distinctive phenotype (within the HPE spectrum) whose primary features include defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and HPE-like midfacial hypoplasia [13].
  • We report four patients with GLI2 mutations together with their associated phenotypes: (1) holoprosencephaly-like phenotype, (2) anophthalmia, branchial arch anomalies, and CNS abnormalities, (3) heminasal aplasia and orbital anomalies, and (4) lobar holoprosencephaly [14].
  • During postnatal mammary development, Gli2 and Gli3 are expressed in stromal and myoepithelial cells, and Gli3 is also found within the lumenal epithelium [15].
 

Associations of GLI2 with chemical compounds

  • A glutathione S-transferase fusion protein of a fragment of Gli2 was able to bind to CREB [16].
  • 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 [17].
  • Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function [18].
  • The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP [19].
  • Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine [19].
 

Physical interactions of GLI2

 

Regulatory relationships of GLI2

  • GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter [12].
  • The results reveal a central role for GLI2 in activating the prosurvival factor BCL2, which may represent an important mechanism in the development or maintenance of cancers associated with inappropriate HH signaling [2].
 

Other interactions of GLI2

  • In normal embryonic kidney tissue, GLI1 and/or GLI2 were bound to each target gene [20].
  • Detailed time-course experiments identified E2F1 as early transcriptional target of GLI2 [11].
  • These data point to a putative role of FOXE1 in mediating Hh signaling in the human epidermis downstream of GLI2 [21].
  • GLI1 and GLI2 are primarily transcriptional activators of Hedgehog target genes, while GLI3 is primarily a transcriptional repressor of Hedgehog targets [22].
  • This long FU and a much shorter isoform were compared for the ability to regulate GLI1 and GLI2 [23].
 

Analytical, diagnostic and therapeutic context of GLI2

  • The ability of THP to prevent complement activation in diluted serum or plasma incubated at 37 degrees C was assessed using both a haemolytic assay with antibody-sensitized sheep RBC and a C4d ELISA [24].
  • A method for direct determination of DL-tetrahydropalmatine (DL-THP) in Corydalis yanhusuo, a traditional Chinese herb, by L-THP imprinted monolithic precolumn on-line/off-line coupling with reversed-phase high performance liquid chromatography (RP-HPLC) was developed [25].
  • GLI2 (GLI-Kruppel family member GLI2) was identified as a positional candidate gene based on comparative mapping; radiation hybrid mapping confirmed that this locus is located within the QTL region [26].
  • Western blot analysis confirmed the presence of nitrated amino acid 3-nitrotyrosine in stone formers, which could bring about structural and functional modifications of THP in hyperoxaluric patients [27].
  • Upon salt precipitation and lyophilization, elution from a Sepharose 4B column revealed one major peak (peak A, cross-reacting with polyclonal anti-THP antibody) and a second minor peak (peak B, not cross-reacting) [28].

References

  1. 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]
  2. 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]
  3. Gli2 is targeted for ubiquitination and degradation by beta-TrCP ubiquitin ligase. Bhatia, N., Thiyagarajan, S., Elcheva, I., Saleem, M., Dlugosz, A., Mukhtar, H., Spiegelman, V.S. J. Biol. Chem. (2006) [Pubmed]
  4. 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]
  5. Hemizygosity for chromosome 2q14.2-q22.1 spanning the GLI2 and PROC genes associated with growth hormone deficiency, polydactyly, deep vein thrombosis and urogenital abnormalities. Gustavsson, P., Schoumans, J., Staaf, J., Jönsson, G., Carlsson, F., Kristoffersson, U., Borg, A., Nordenskjöld, M., Dahl, N. Clin. Genet. (2006) [Pubmed]
  6. GLI2 knockdown using an antisense oligonucleotide induces apoptosis and chemosensitizes cells to paclitaxel in androgen-independent prostate cancer. Narita, S., So, A., Ettinger, S., Hayashi, N., Muramaki, M., Fazli, L., Kim, Y., Gleave, M.E. Clin. Cancer Res. (2008) [Pubmed]
  7. Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus. El Andaloussi, A., Graves, S., Meng, F., Mandal, M., Mashayekhi, M., Aifantis, I. Nat. Immunol. (2006) [Pubmed]
  8. Reversal of neurosteroid effects at alpha4beta2delta GABA(A) receptors triggers anxiety at puberty. Shen, H., Gong, Q.H., Aoki, C., Yuan, M., Ruderman, Y., Dattilo, M., Williams, K., Smith, S.S. Nat. Neurosci. (2007) [Pubmed]
  9. Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling. Riobó, N.A., Lu, K., Ai, X., Haines, G.M., Emerson, C.P. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Concurrent chemoradiotherapy with cyclophosphamide, pirarubicin, and cisplatin for patients with locally advanced salivary gland carcinoma. Katori, H., Tsukuda, M. Acta Otolaryngol. (2006) [Pubmed]
  11. The zinc-finger transcription factor GLI2 antagonizes contact inhibition and differentiation of human epidermal cells. Regl, G., Kasper, M., Schnidar, H., Eichberger, T., Neill, G.W., Ikram, M.S., Quinn, A.G., Philpott, M.P., Frischauf, A.M., Aberger, F. Oncogene (2004) [Pubmed]
  12. 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]
  13. Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. Roessler, E., Du, Y.Z., Mullor, J.L., Casas, E., Allen, W.P., Gillessen-Kaesbach, G., Roeder, E.R., Ming, J.E., Ruiz i Altaba, A., Muenke, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. GLI2 mutations in four Brazilian patients: How wide is the phenotypic spectrum? Rahimov, F., Ribeiro, L.A., de Miranda, E., Richieri-Costa, A., Murray, J.C. Am. J. Med. Genet. A (2006) [Pubmed]
  15. Gli3-mediated repression of Hedgehog targets is required for normal mammary development. Hatsell, S.J., Cowin, P. Development (2006) [Pubmed]
  16. 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. Dan, S., Tanimura, A., Yoshida, M. J. Virol. (1999) [Pubmed]
  17. 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]
  18. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. Haycraft, C.J., Banizs, B., Aydin-Son, Y., Zhang, Q., Michaud, E.J., Yoder, B.K. PLoS Genet. (2005) [Pubmed]
  19. Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors. Huang, H.S., Chen, J., Chen, C.F., Ma, M.C. Kidney Int. (2006) [Pubmed]
  20. 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]
  21. 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]
  22. Asymmetric expression of Gli transcription factors in Hensen's node. Granata, A., Quaderi, N.A. Gene Expr. Patterns (2005) [Pubmed]
  23. 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]
  24. Importance of carbohydrate in the interaction of Tamm-Horsfall protein with complement 1q and inhibition of classical complement activation. Rhodes, D.C. Immunol. Cell Biol. (2006) [Pubmed]
  25. Determination of DL-tetrahydropalmatine in Corydalis yanhusuo by L-tetrahydropalmatine imprinted monolithic column coupling with reversed-phase high performance liquid chromatography. Ou, J., Kong, L., Pan, C., Su, X., Lei, X., Zou, H. Journal of chromatography. A. (2006) [Pubmed]
  26. Genetic analysis of anal atresia in pigs: evidence for segregation at two main loci. Cassini, P., Montironi, A., Botti, S., Hori, T., Okhawa, H., Stella, A., Andersson, L., Giuffra, E. Mamm. Genome (2005) [Pubmed]
  27. Immunological detection of nitrosative stress-mediated modified Tamm-Horsfall glycoprotein (THP) in calcium oxalate stone formers. Pragasam, V., Kalaiselvi, P., Sumitra, K., Srinivasan, S., Anandkumar, P., Varalakshmi, P. Biomarkers (2006) [Pubmed]
  28. Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function. Jaggi, M., Nakagawa, Y., Zipperle, L., Hess, B. Urol. Res. (2007) [Pubmed]
 
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