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Gene Review

l(2)gl  -  lethal (2) giant larvae

Drosophila melanogaster

Synonyms: CG2671, D-LGL, Dmel\CG2671, L(2)GL, L(2)gl, ...
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Disease relevance of l(2)gl

  • Analysis of metastasis patterns of the lines containing P element insertions and lacking wild-type l(2)gl expression identified three homozygous mutations that dramatically alter tumorigenesis and/or metastasis [1].
  • Recessive mutations at the lethal(2)giant larvae (l(2)gl) locus of Drosophila melanogaster cause a complex syndrome, which has as its most striking features the development of malignant neuroblastomas in the larval brain and tumors of the imaginal discs [2].
  • Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer [3].
  • While mutations in both lgl and brat cause neoplastic brain tumors, our results reveal that metastatic cells arising from these tumors have quite different properties [4].

Psychiatry related information on l(2)gl

  • These phenotypes are accompanied by an arrest of the cell shape changes normally occurring in lateral epidermis and in epithelial midgut cells. l(2)gl activity is also necessary for larval fife and the critical period falls within the third instar larval stage [5].

High impact information on l(2)gl


Biological context of l(2)gl

  • Random homozygous P element insertions were screened for the ability to modulate the l(2)gl phenotype [1].
  • Phospho-Mad and the downstream target gene vestigial were elevated in l(2)gl tumors, thus linking Drosophila neoplasia to the Dpp (TGF-beta-like) signal pathway [1].
  • The transgene can fully rescue the development of l(2)gl flies raised at 22 degrees C but causes drastic effects on their development at 29 degrees C confirming the temperature sensitivity of the phenylalanine substitution at position 311 [10].
  • These findings confirm that p127 is a component of a cytoskeletal network including myosin and suggest that the neoplastic transformation resulting from l(2)gl gene inactivation may be caused by the partial disruption of this network [11].
  • The Drosophila tumor suppressor protein lethal (2) giant larvae (l(2)gl) is involved in asymmetric cell division during development and epithelial cell polarity through interaction with the aPKC.Par-6 complex [12].

Anatomical context of l(2)gl

  • Our investigations into the l(2)gl function have revealed that the gene product, or p127 protein, acts as a cytoskeletal protein distributed in both the cytoplasm and on the inner face of lateral cell membranes in a number of tissues throughout development [11].
  • Inactivation of the Drosophila lethal(2)giant larvae (l(2)gl) gene causes malignant tumors in the brain and the imaginal discs and produces developmental abnormalities in other tissues, including the germline, the ring gland and the salivary glands [11].
  • Stoichiometric levels of zipper and l(2)gl are required for proper segregation of cellular determinants during neuroblast stem cell division [13].
  • Moreover, we show that crb and lgl cooperate in zonula adherens formation early in development [14].
  • These data indicate that during oogenesis p127 plays a critical function at the onset of vitellogenesis and regulates growth of the oocyte, follicle cell migration over the oocyte and their organization in a palisadic epithelium, as well as viability of the germline cells [10].

Associations of l(2)gl with chemical compounds

  • This dissociation can be inhibited by staurosporine and a 26mer peptide covering amino acid positions 651 to 676 of p127 and containing five serine residues which are evolutionarily conserved from Drosophila to humans [15].

Physical interactions of l(2)gl


Regulatory relationships of l(2)gl


Other interactions of l(2)gl


Analytical, diagnostic and therapeutic context of l(2)gl


  1. Drosophila screening model for metastasis: Semaphorin 5c is required for l(2)gl cancer phenotype. Woodhouse, E.C., Fisher, A., Bandle, R.W., Bryant-Greenwood, B., Charboneau, L., Petricoin, E.F., Liotta, L.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. Mechler, B.M., McGinnis, W., Gehring, W.J. EMBO J. (1985) [Pubmed]
  3. Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Schimanski, C.C., Schmitz, G., Kashyap, A., Bosserhoff, A.K., Bataille, F., Schäfer, S.C., Lehr, H.A., Berger, M.R., Galle, P.R., Strand, S., Strand, D. Oncogene (2005) [Pubmed]
  4. Drosophila brain tumor metastases express both neuronal and glial cell type markers. Beaucher, M., Goodliffe, J., Hersperger, E., Trunova, S., Frydman, H., Shearn, A. Dev. Biol. (2007) [Pubmed]
  5. The tumor suppressor gene, lethal(2)giant larvae (1(2)g1), is required for cell shape change of epithelial cells during Drosophila development. Manfruelli, P., Arquier, N., Hanratty, W.P., Sémériva, M. Development (1996) [Pubmed]
  6. Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Betschinger, J., Mechtler, K., Knoblich, J.A. Cell (2006) [Pubmed]
  7. Structure of the l(2)gl gene of Drosophila and delimitation of its tumor suppressor domain. Jacob, L., Opper, M., Metzroth, B., Phannavong, B., Mechler, B.M. Cell (1987) [Pubmed]
  8. The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Peng, C.Y., Manning, L., Albertson, R., Doe, C.Q. Nature (2000) [Pubmed]
  9. A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl controlled by Hox-C8 in vivo. Tomotsune, D., Shoji, H., Wakamatsu, Y., Kondoh, H., Takahashi, N. Nature (1993) [Pubmed]
  10. Requirement of Drosophila I(2)gl function for survival of the germline cells and organization of the follicle cells in a columnar epithelium during oogenesis. De Lorenzo, C., Strand, D., Mechler, B.M. Int. J. Dev. Biol. (1999) [Pubmed]
  11. The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. Strand, D., Jakobs, R., Merdes, G., Neumann, B., Kalmes, A., Heid, H.W., Husmann, I., Mechler, B.M. J. Cell Biol. (1994) [Pubmed]
  12. Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division. Yasumi, M., Sakisaka, T., Hoshino, T., Kimura, T., Sakamoto, Y., Yamanaka, T., Ohno, S., Takai, Y. J. Biol. Chem. (2005) [Pubmed]
  13. Induced paternal effects mimic cytoplasmic incompatibility in Drosophila. Clark, M.E., Heath, B.D., Anderson, C.L., Karr, T.L. Genetics (2006) [Pubmed]
  14. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Tanentzapf, G., Tepass, U. Nat. Cell Biol. (2003) [Pubmed]
  15. A serine-kinase associated with the p127-l(2)gl tumour suppressor of Drosophila may regulate the binding of p127 to nonmuscle myosin II heavy chain and the attachment of p127 to the plasma membrane. Kalmes, A., Merdes, G., Neumann, B., Strand, D., Mechler, B.M. J. Cell. Sci. (1996) [Pubmed]
  16. Lethal giant larvae controls the localization of notch-signaling regulators numb, neuralized, and Sanpodo in Drosophila sensory-organ precursor cells. Langevin, J., Le Borgne, R., Rosenfeld, F., Gho, M., Schweisguth, F., Bellaïche, Y. Curr. Biol. (2005) [Pubmed]
  17. Transcription of Dfos is stimulated by brain tumours of l(2)gl-deficient larvae of Drosophila melanogaster. Nedelcheva, M., Topouzova, T., Genova, G. Int. J. Biochem. Cell Biol. (2001) [Pubmed]
  18. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Bilder, D., Li, M., Perrimon, N. Science (2000) [Pubmed]
  19. The Drosophila tumor suppressor gene lethal(2)giant larvae is required for the emission of the Decapentaplegic signal. Arquier, N., Perrin, L., Manfruelli, P., Sémériva, M. Development (2001) [Pubmed]
  20. The Drosophila melanogaster l(2)gl gene encodes a protein homologous to the cadherin cell-adhesion molecule family. Klämbt, C., Müller, S., Lützelschwab, R., Rossa, R., Totzke, F., Schmidt, O. Dev. Biol. (1989) [Pubmed]
  21. The rgl-1 is a legitimate homologue of lethal giant larvae recessive oncogene in rat. Kim, Y.S., Baek, K.H., Lee, K.Y., Chung, H.M., Lee, K.A., Ko, J.J., Cha, K.Y. Int. J. Oncol. (2002) [Pubmed]
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