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arm  -  armadillo

Drosophila melanogaster

Synonyms: ARM, Arm, Armadillo segment polarity protein, CG11579, Dm Arm, ...
 
 
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Disease relevance of arm

  • In mammals, constitutive beta-catenin causes over-proliferation and abnormal differentiation of skin cells, resulting in skin cancer formation [1].
  • We found that SHARP gene and protein expression is elevated in human colon and ovarian endometrioid adenocarcinomas and mouse colon adenomas and carcinomas carrying gene defects leading to beta-catenin dysregulation [2].
  • These mutations on their own cause increased stabilization of Armadillo and cuticle pattern disruptions that include replacement of ventral denticles with naked cuticle, which suggests that the mutant embryos suffer from ectopic Wg pathway activation [3].
  • We previously reported that expression of WNT7a, encoded on 3p25, was frequently downregulated in lung cancer, and that loss of E-cadherin or beta-catenin was a poor prognostic feature [4].
  • It was then speculated that HBx, a viral regulatory protein of HBV, is involved in activating Wnt/beta-catenin signaling in hepatoma cells [5].
 

High impact information on arm

  • Its activation entails the association of beta-catenin with nuclear TCF/LEF proteins and results in transcriptional activation of target genes [6].
  • Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism [7].
  • Our results suggest that the recruitment of Pygo permits beta-catenin to transcriptionally activate Wnt target genes and raise the possibility that a deregulation of these events may play a causal role in the development of B cell malignancies [8].
  • Here, we present findings, which challenge this view and suggest instead that beta-catenin may transduce Wnt signals by exporting TCF from the nucleus or activating it in the cytoplasm [9].
  • The structure reveals an extended, rainbow shaped molecule, with tandem helical repeats that bear unexpected resemblance to the armadillo repeats in beta-catenin and the HEAT repeats in protein phosphatase 2A [10].
 

Biological context of arm

 

Anatomical context of arm

 

Associations of arm with chemical compounds

 

Physical interactions of arm

 

Enzymatic interactions of arm

  • In the absence of Wnt ligand, beta-catenin is phosphorylated by the Axin complex, which earmarks it for rapid degradation by the ubiquitin system [29].
  • Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila [30].
 

Co-localisations of arm

 

Regulatory relationships of arm

  • Levels of cytoplasmic Armadillo are also regulated by Zeste-White 3 kinase [32].
  • Various mutant conditions that cause dissociation of E-APC from these zones also obliterate the segmental modulation of free Armadillo levels that is normally induced by Wingless signalling [16].
  • Genetic evidence that Drosophila frizzled controls planar cell polarity and Armadillo signaling by a common mechanism [33].
  • In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential [34].
  • However, recent findings in Drosophila indicated that Armadillo may activate dTCF in the cytoplasm [35].
 

Other interactions of arm

  • In the embryonic epidermis, Wg protein is secreted and taken up by neighboring cells, in which it is required for maintenance of engrailed transcription and accumulation of Armadillo protein [36].
  • We found that E-cadherin and Armadillo (Arm, Drosophila beta-catenin) protein levels were specifically reduced in cells lacking MyoVI, whereas other proteins were not [37].
  • Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function [11].
  • Notably, linking Armadillo to a nuclear localization sequence rescues pygo and lgs mutant fly embryos [11].
  • Finally, we present data implicating kinases in addition to Zeste white-3 in Armadillo phosphorylation [13].
 

Analytical, diagnostic and therapeutic context of arm

References

  1. Wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila. Song, X., Xie, T. Development (2003) [Pubmed]
  2. Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. Feng, Y., Bommer, G.T., Zhai, Y., Akyol, A., Hinoi, T., Winer, I., Lin, H.V., Cadigan, K.M., Cho, K.R., Fearon, E.R. Cancer Res. (2007) [Pubmed]
  3. RacGap50C negatively regulates wingless pathway activity during Drosophila embryonic development. Jones, W.M., Bejsovec, A. Genetics (2005) [Pubmed]
  4. WNT7a induces E-cadherin in lung cancer cells. Ohira, T., Gemmill, R.M., Ferguson, K., Kusy, S., Roche, J., Brambilla, E., Zeng, C., Baron, A., Bemis, L., Erickson, P., Wilder, E., Rustgi, A., Kitajewski, J., Gabrielson, E., Bremnes, R., Franklin, W., Drabkin, H.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Hepatitis B virus X protein is essential for the activation of Wnt/beta-catenin signaling in hepatoma cells. Cha, M.Y., Kim, C.M., Park, Y.M., Ryu, W.S. Hepatology (2004) [Pubmed]
  6. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo. Mosimann, C., Hausmann, G., Basler, K. Cell (2006) [Pubmed]
  7. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Liu, C., Li, Y., Semenov, M., Han, C., Baeg, G.H., Tan, Y., Zhang, Z., Lin, X., He, X. Cell (2002) [Pubmed]
  8. Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Kramps, T., Peter, O., Brunner, E., Nellen, D., Froesch, B., Chatterjee, S., Murone, M., Züllig, S., Basler, K. Cell (2002) [Pubmed]
  9. Evidence that Armadillo transduces wingless by mediating nuclear export or cytosolic activation of Pangolin. Chan, S.K., Struhl, G. Cell (2002) [Pubmed]
  10. Structure of Pumilio reveals similarity between RNA and peptide binding motifs. Edwards, T.A., Pyle, S.E., Wharton, R.P., Aggarwal, A.K. Cell (2001) [Pubmed]
  11. Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function. Townsley, F.M., Cliffe, A., Bienz, M. Nat. Cell Biol. (2004) [Pubmed]
  12. The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Daniel, J.M., Reynolds, A.B. Mol. Cell. Biol. (1999) [Pubmed]
  13. Negative regulation of Armadillo, a Wingless effector in Drosophila. Pai, L.M., Orsulic, S., Bejsovec, A., Peifer, M. Development (1997) [Pubmed]
  14. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Parker, D.S., Jemison, J., Cadigan, K.M. Development (2002) [Pubmed]
  15. Cadherin sequences that inhibit beta-catenin signaling: a study in yeast and mammalian cells. Simcha, I., Kirkpatrick, C., Sadot, E., Shtutman, M., Polevoy, G., Geiger, B., Peifer, M., Ben-Ze'ev, A. Mol. Biol. Cell (2001) [Pubmed]
  16. A new Drosophila APC homologue associated with adhesive zones of epithelial cells. Yu, X., Waltzer, L., Bienz, M. Nat. Cell Biol. (1999) [Pubmed]
  17. Roles of Armadillo, a Drosophila catenin, during central nervous system development. Loureiro, J., Peifer, M. Curr. Biol. (1998) [Pubmed]
  18. Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Huber, O., Korn, R., McLaughlin, J., Ohsugi, M., Herrmann, B.G., Kemler, R. Mech. Dev. (1996) [Pubmed]
  19. Phenotypic analysis of null mutants for DE-cadherin and Armadillo in Drosophila ovaries reveals distinct aspects of their functions in cell adhesion and cytoskeletal organization. Oda, H., Uemura, T., Takeichi, M. Genes Cells (1997) [Pubmed]
  20. Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. Langevin, J., Morgan, M.J., Sibarita, J.B., Aresta, S., Murthy, M., Schwarz, T., Camonis, J., Bellaïche, Y. Dev. Cell (2005) [Pubmed]
  21. The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction. Peifer, M. J. Cell. Sci. (1993) [Pubmed]
  22. The role of cell adhesion molecules in Drosophila heart morphogenesis: faint sausage, shotgun/DE-cadherin, and laminin A are required for discrete stages in heart development. Haag, T.A., Haag, N.P., Lekven, A.C., Hartenstein, V. Dev. Biol. (1999) [Pubmed]
  23. The role of the cysteine-rich domain of Frizzled in Wingless-Armadillo signaling. Povelones, M., Nusse, R. EMBO J. (2005) [Pubmed]
  24. Alteration of matrix glycosaminoglycans diminishes articular chondrocytes' response to a canonical Wnt signal. Shortkroff, S., Yates, K.E. Osteoarthr. Cartil. (2007) [Pubmed]
  25. Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo. Pai, L.M., Kirkpatrick, C., Blanton, J., Oda, H., Takeichi, M., Peifer, M. J. Biol. Chem. (1996) [Pubmed]
  26. The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila. Gallet, A., Angelats, C., Erkner, A., Charroux, B., Fasano, L., Kerridge, S. EMBO J. (1999) [Pubmed]
  27. Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin. Hamada, F., Tomoyasu, Y., Takatsu, Y., Nakamura, M., Nagai, S., Suzuki, A., Fujita, F., Shibuya, H., Toyoshima, K., Ueno, N., Akiyama, T. Science (1999) [Pubmed]
  28. Neuroglian and DE-cadherin activate independent cytoskeleton assembly pathways in Drosophila S2 cells. Dubreuil, R.R., Grushko, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  29. A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling. Cliffe, A., Hamada, F., Bienz, M. Curr. Biol. (2003) [Pubmed]
  30. Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila. Yanagawa, S., Matsuda, Y., Lee, J.S., Matsubayashi, H., Sese, S., Kadowaki, T., Ishimoto, A. EMBO J. (2002) [Pubmed]
  31. The Drosophila rhomboid protein is concentrated in patches at the apical cell surface. Sturtevant, M.A., Roark, M., O'Neill, J.W., Biehs, B., Colley, N., Bier, E. Dev. Biol. (1996) [Pubmed]
  32. wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Peifer, M., Sweeton, D., Casey, M., Wieschaus, E. Development (1994) [Pubmed]
  33. Genetic evidence that Drosophila frizzled controls planar cell polarity and Armadillo signaling by a common mechanism. Povelones, M., Howes, R., Fish, M., Nusse, R. Genetics (2005) [Pubmed]
  34. Roles of the C terminus of Armadillo in Wingless signaling in Drosophila. Cox, R.T., Pai, L.M., Kirkpatrick, C., Stein, J., Peifer, M. Genetics (1999) [Pubmed]
  35. A complex of Armadillo, Legless, and Pygopus coactivates dTCF to activate wingless target genes. Thompson, B.J. Curr. Biol. (2004) [Pubmed]
  36. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Klingensmith, J., Nusse, R., Perrimon, N. Genes Dev. (1994) [Pubmed]
  37. Myosin VI is required for E-cadherin-mediated border cell migration. Geisbrecht, E.R., Montell, D.J. Nat. Cell Biol. (2002) [Pubmed]
  38. A Drosophila Axin homolog, Daxin, inhibits Wnt signaling. Willert, K., Logan, C.Y., Arora, A., Fish, M., Nusse, R. Development (1999) [Pubmed]
  39. Studies on human colon cancer gene APC by targeted expression in Drosophila. Bhandari, P., Shashidhara, L.S. Oncogene (2001) [Pubmed]
  40. Interaction between EGFR signaling and DE-cadherin during nervous system morphogenesis. Dumstrei, K., Wang, F., Shy, D., Tepass, U., Hartenstein, V. Development (2002) [Pubmed]
  41. CKIepsilon/discs overgrown promotes both Wnt-Fz/beta-catenin and Fz/PCP signaling in Drosophila. Klein, T.J., Jenny, A., Djiane, A., Mlodzik, M. Curr. Biol. (2006) [Pubmed]
 
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