Current Science

Open Access Open Access  Restricted Access Subscription Access

Crumbs Top and ‘Notch’ed Bottom in Tumours


Affiliations
1 Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine, New Brunswick, Saint John, NB, E2L4L5, Canada
2 Chemical Biology Laboratory, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, India
3 Department of Biochemistry, Central University of Haryana, Mahendergarh 123 029, India
 

Membrane-bound proteins integrate and coordinate various signalling activities to maintain tissue architecture. In recent years, research updates indicate that these proteins undergo post-translational modification like glycosylation to maintain tissue integrity. Here we discuss research updates from Drosophila, about two essential membrane-bound proteins, Notch and Crumbs, that undergo such modifications to interact with each other and their implications in tumorigenesis

Keywords

Epidermal-Growth-Factor Repeats, Glycosyltransferases, Membrane-Bound Proteins, Tumorigenesis, Xylosylation.
User
Notifications
Font Size

  • Bray, S. J., A simple pathway becomes complex. Nature Rev. Mol. Cell Biol., 2006, 7(9), 678–689.

  • Etienne-Manneville, S., Polarity proteins in migration and invasion. Oncogene, 2008, 27(55), 6970–6980.

  • Nowell, C. S. and Radtke, F., Notch as a tumour suppressor. Nature Rev. Cancer, 2017, 17(3), 145–159.

  • Yuan, X. et al., Notch signaling: an emerging therapeutic target for cancer treatment. Cancer Lett., 2015, 369(1), 20–27.

  • Ntziachristos, P., Lim, J. S., Sage, J. and Aifantis, I., From fly wings to targeted cancer therapies: a centennial for notch signaling. Cancer Cell, 2014, 25(3), 318–334.

  • Liu, J., Shen, J., Wen, X., Guo, Y. and Zhang, G., Targeting notch degradation system provides promise for breast cancer therapeutics. Crit. Rev. Oncol. Hematol., 2016, 104, 21–29.

  • Martin-Belmonte, F. and Perez-Moreno M., Epithelial cell polarity, stem cells and cancer. Nature Rev. Cancer, 2012, 12(1), 23–38.

  • Ellenbroek, S. I., Iden, S. and Collard, J. G., Cell polarity proteins and cancer. Sem. Cancer Biol., 2012, 22(3), 208–215.

  • Bergstralh, D. T. and St Johnston, D., Epithelial cell polarity: what flies can teach us about cancer. Essays Biochem., 2012, 53, 129–140.

  • Lin, W. H., Asmann, Y. W. and Anastasiadis, P. Z., Expression of polarity genes in human cancer. Cancer Informat., 2015, 30, 15–28.

  • Lobry, C., Oh, P. and Aifantis, I., Oncogenic and tumor suppressor functions of notch in cancer: it’s NOTCH what you think. J. Exp. Med., 2011, 208(10), 1931–1935.

  • Pakkiriswami, S., Couto, A., Nagarajan, U. and Georgiou, M., Glycosylated notch and cancer. Front. Oncol., 2016, 6, 37.

  • Herranz, H., Stamataki, E., Feiguin, F. and Milán, M., Selfrefinement of notch activity through the transmembrane protein crumbs: modulation of gamma-secretase activity. EMBO Rep., 2006, 7(3), 297–302.

  • Vermezovic, J. et al., Notch is a direct negative regulator of the DNA-damage response. Nature Struct. Mol. Biol., 2015, 22, 417–424.

  • Das, S. and Knust, E., A dual role of the extracellular domain of Drosophila crumbs formorphogenesis of the embryonic neuroectoderm. Biol. Open, 2018, 7, bio031435.

  • Baron, M., Combining genetic and biophysical approaches to probe the structure and function relationships of the Notch receptor. Mol. Membr. Biol., 2019, 3, 33–49.

  • Tepass, U., Theres, C. and Knust, E., Crumbs encodes an EGFlike protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell, 1990, 61(5), 787–799.

  • Laprise, P., Emerging role for epithelial polarity proteins of the crumbs family as potential tumor suppressors. J. Biomed. Biotechnol., 2011, 1, 868217.

  • Nemetschke, L. and Knust, E., Drosophila Crumbs prevents ectopic Notch activation in developing wings by inhibiting ligand-independent endocytosis. Development, 2016, 143(23), 4543–4553.

  • Jin, G., Cao, Z., Sun, X., Wang, K., Huang, T. and Shen, B., Protein O-glucosyltransferase 1 overexpression downregulates p16 in BT474 human breast cancer cells. Oncol. Lett., 2014, 8(2), 594–600.

  • Ramkumar, N. et al., Protein O-glucosyltransferase 1 (POGLUT1) promotes mouse gastrulation through modification of the apical polarity protein CRUMBS2. PLoS Genet., 2015, 11(10), e1005551.

  • Li, P. et al., CRB3 downregulation confers breast cancer stem cell traits through TAZ/β -catenin. Oncogenesis, 2017, 6(4), e322.

  • Wharton, K. A., Johansen, K. M., Xu, T. and Artavanis-Tsakonas, S., Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGFlike repeats. Cell, 1985, 43, 567–581.

  • Tepass, U. and Knust, E., Phenotypic and developmental analysis of mutations at the Crumbs locus, a gene required for the development of epithelia in Drosophila melanogaster. Roux’s Arch. Dev. Biol.: Off. Organ EDBO, 1990, 99(4), 189–206.

  • Frappaolo, A., Sechi, S., Kumagai, T., Karimpour-Ghahnavieh, A., Tiemeyer, M. and Giansanti, M. G., Modeling congenital disorders of N-linked glycoprotein glycosylation in Drosophila melanogaster. Front. Genet., 2018, 9, 436.

  • Hori, K., Sen, A. and Artavanis-Tsakonas, S., Notch signaling at a glance. J. Cell Sci., 2013, 126, 2135–2140.

  • del Álamo, D., Rouault, H. and Schweisguth, F., Mechanism and significance of cis-inhibition in Notch signalling. Curr. Biol., 2011, 21(1), R40–R47.

  • Gordon, W. R., Arnett, K. L. and Blacklow, S. C., The molecular logic of notch signaling –a structural and biochemical perspective. J. Cell Sci., 2008, 121, 3109–3119.

  • Antfolk, D., Antila, C., Kemppainen, K., Landor, S. K. J. and Sahlgren, C., Decoding the PTM-switchboard of Notch. Acta (BBA) –Mol. Cell Res., 2019, 1866, 118507.

  • Lee, T. V., Pandey, A. and Jafar-Nejad, H., Xylosylation of the Notch receptor preserves the balance between its activation by trans-delta and inhibition by cis-ligands in Drosophila. PLoS Genet., 2017, 13(4), e1006723.

  • Kakuda, S. and Haltiwanger, R. S., Deciphering the fringe-mediated Notch code: identification of activating and inhibiting sites allowing discrimination between ligands. Dev. Cell, 2017, 40(2), 193–201.

  • Kumichel, A., Katja, K. and Knust, E., A conserved di-basic motif of Drosophila Crumbs contributes to efficient ER export. Traffic, 2015, 16(6), 604–616.

  • Li, P., Mao, X., Ren, Y. and Liu, P., Epithelial cell polarity determinant CRB3 in cancer development. Int. J. Biol. Sci., 2015 11(1), 31–37.

  • Pellissier, L. P. et al., Targeted ablation of Crb1 and Crb2 in retinal progenitor cells mimics Leber congenital amaurosis. PLoS Genet., 2013, 9(12), e1003976.

  • Richardson, E. C. N. and Pichaud, F., Crumbs is required to achieve proper organ size control during Drosophila head development. Development, 2010, 137(4), 641–650.

  • Ohata, S. et al., Dual roles of Notch in regulation of apically restricted mitosis and apicobasal polarity of neuroepithelial cells. Neuron, 2011, 69(2), 215–230.

  • Koles, K., Lim, J., Aoki, K., Porterfield, M., Tiemeyer, M., Wells, L. and Panin, V., Identification of N-glycosylated proteins from the central nervous system of Drosophila melanogaster. Glycobiology, 2007, 17(12), 1388–1403.

  • Zielinska, D. F., Gnad, F., Schropp, K., Wiśniewski, J. R. and Mann, M., Mapping N-glycosylation sites across seven evolutionarily distant species reveals a divergent substrate proteome despite a common core machinery. Mol. Cell, 2012, 46(4), 542–548.

  • Cordle, J. et al., A conserved face of the jagged/serrate DSL domain is involved in notch trans-activation and cis-inhibition. Nature Struct. Mol. Biol., 2008, 15(8), 849–857.

  • Weisshuhn, P. C., Sheppard, D., Taylor, P., Whiteman, P., Lea, S. M., Handford, P. A. and Redfield, C., Non-linear and flexible regions of the human Notch1 extracellular domain revealed by highresolution structural studies. Structure, 2016, 24(4), 555–566.

  • Malecki, M. J., Sanchez-Irizarry, C., Mitchell, J. L, Histen, G., Xu, M. L., Aster, J. C. and Blacklow, S C., Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes. Mol. Cell. Biol., 2006, 26(12), 4642–4651.

  • Li, Z., Fischer, M., Satkunarajah, M., Zhou, D., Withers, S. G. and Rini, J. M., Structural basis of notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1). Nature Commun., 2017, 8(1), 185.

  • Weng, A. P. et al., Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science, 2004, 6(5694), 269–271.

  • Li, K. et al., Modulation of notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J. Biol. Chem., 2008, 283(12), 8046–8054.


Abstract Views: 416

PDF Views: 129




  • Crumbs Top and ‘Notch’ed Bottom in Tumours

Abstract Views: 416  |  PDF Views: 129

Authors

Shanmugasundaram Pakkiriswami
Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine, New Brunswick, Saint John, NB, E2L4L5, Canada
Sampath Natarajan
Chemical Biology Laboratory, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, India
Usha Nagarajan
Department of Biochemistry, Central University of Haryana, Mahendergarh 123 029, India

Abstract


Membrane-bound proteins integrate and coordinate various signalling activities to maintain tissue architecture. In recent years, research updates indicate that these proteins undergo post-translational modification like glycosylation to maintain tissue integrity. Here we discuss research updates from Drosophila, about two essential membrane-bound proteins, Notch and Crumbs, that undergo such modifications to interact with each other and their implications in tumorigenesis

Keywords


Epidermal-Growth-Factor Repeats, Glycosyltransferases, Membrane-Bound Proteins, Tumorigenesis, Xylosylation.

References





DOI: https://doi.org/10.18520/cs%2Fv121%2Fi10%2F1297-1301