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Interaction of Bcl-Abl Oncoprotein with the Glg1 Protein in K562 Cells: its Role in the Pathogenesis of Chronic Myeloid Leukemia

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Abstract

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease characterized by the occurrence of the Bcr-Abl fusion oncoprotein, which resulted from a reciprocal translocation between chromosomes 9 and 22. The Golgi complex-localized protein 1(GLG1) was identified by mass spectrometry as a potential interaction partner to the pleckstrin homology (PH) domain of the Bcr-Abl oncoprotein. The GLG1 protein is a transmembrane protein known also as MG-160, ESL-1, and CFR-1. Irregularities in the GLG1 functions affect the adhesion, mobility, and migration of cells. In this study, the interaction between the GLG1 protein and the Bcr-Abl oncoprotein is shown for the first time. With imunofluorescence and confocal microscopy, colocalization of the GLG1protein and the Bcr-Abl oncoprotein to the Golgi complex has been detected. A GLG1 protein form phosphorylated at the tyrosine site in K562 cells has also been detected, and Tyr phosphorylation sites for GLG1 isoforms were predicted. The authors believe that the oncoprotein phosphorylates the GLG1 protein, at the cost of its Abl part, during the GLG1–Bcr-Abl protein interaction in the Golgi complex, thus affecting its activity and disrupting the descending signaling pathways that may be crucial for the development and progression of the disease.

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REFERENCES

  1. Salem, A., Loghavi, S., Tang, G., Huh, Y.O., Jabbour, E.J., Kantarjian, H., Wang, W., Hu, S., Luthra, R., Medeiros, L.J., and Khoury, J.D., Myeloid neoplasms with concurrent BCR-ABL1 and CBFB rearrangements: a series of 10 cases of a clinically aggressive neoplasm, Am. J. Hematol., 2017, vol. 92, no. 6, pp. 520–528.https://doi.org/10.1002/ajh.24710

    Article  CAS  Google Scholar 

  2. Flis, S. and Chojnacki, T., Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities, Drug. Design. Dev. Ther., 2019, vol. 13, pp. 825–843. https://doi.org/10.2147/DDDT.S191303

    Article  CAS  Google Scholar 

  3. Telegeev, G.D., Dubrovska, V.A., Nadgorna, V.A., Dybkov, M.V., Zavelevich, M.P., Maliuta, S.S., and Gluzman, D.F., Immunocytochemical study of Bcr and Bcr-Abl localization in K562 cells, Exp. Oncol., 2010, vol. 32, no. 2, pp. 81–83.

    CAS  PubMed  Google Scholar 

  4. Quintás-Cardama, A. and Cortes, J., Molecular biology of bcr-abl1-positive chronic myeloid leukemia, Blood, 2009, vol. 113, pp. 1619–1630. https://doi.org/10.1182/blood-2008-03-144790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ross, T.S. and Mgbemena, V.E., Re-evaluating the role of BCR/ABL in chronic myelogenous leukemia, Mol Cell Oncol., 2014, vol. 1, no. 3, p. 963450. https://doi.org/10.4161/23723548.2014.963450

    Article  CAS  Google Scholar 

  6. Järas, M., Johnels, P., Agerstam, H., Lassen, C., Rissler, M., and Edén, P., Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage, Exp. Hematol., 2009, vol. 37, no. 3. pp. 367–375. https://doi.org/10.1016/j.exphem.2008.11.003

    Article  CAS  PubMed  Google Scholar 

  7. Aladag, E. and Haznedaroğlu, I.C., Current perspectives for the treatment of chronic myeloid leukemia, Turc. J. Med. Sci., 2019, vol. 11, no. 49 (1), pp. 1–10. https://doi.org/10.3906/sag-1810-81

  8. Colicelli, J., ABL tyrosine kinases: evolution of function, regulation, and specificity, Sci. Signal., 2010, vol. 14, no. 3, pp. 139–141.

    Google Scholar 

  9. Miroshnychenko, D., Dubrovska, A., Maliuta, S., Telegeev, G., and Aspenstrom, P., Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein-protein and protein-lipid interactions, Exp. Cell. Res., 2010, vol. 316, no. 4, pp. 530–542. https://doi.org/10.1016/j.yexcr.2009.11.014

    Article  CAS  PubMed  Google Scholar 

  10. Zarbock, A., Ley, K., McEver, R.P., and Hidalgo, A., Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow, Blood, 2011, vol. 22, no. 118 (26), pp. 6743–6751. https://doi.org/10.1182/blood-2011-07-343566

    Article  CAS  Google Scholar 

  11. Mourelatos, Z., Gonatas, J.O., Cinato, E., and Gonatas, N.K., Cloning and sequence analysis of the human MG160, a fibroblast growth factor and E-selectin binding membrane sialoglycoprotein of the Golgi apparatus, DNA Cell. Biol., 1996, vol. 15, no. 12, pp. 1121–1128.https://doi.org/10.1089/dna.1996.15.1121

    Article  CAS  PubMed  Google Scholar 

  12. Crou, S., Mezitis, S.G., Stieber, A., Gonatas, J.O., Goud, B., and Gonatas, N.K., Immunocytochemical visualization of the Golgi apparatus in several species, including human, and tissues with an antiserum against MG-160, asialoglycoprotein of rat Golgi apparatus, J. Histochem. Cytochem., 1990, vol. 38, no. 7, pp. 957–963. https://doi.org/10.1177/38.7.2355176

    Article  Google Scholar 

  13. Planche, A., Bacac, M., and Stamenkovic, I., The Golgi protein GLG1 participates in tumor progression, Cancer Res., 2012, vol. 72, pp. 3245–3245. https://doi.org/10.1158/1538-7445.AM2012-3245

    Article  Google Scholar 

  14. Yasmin-Karim, S. and King, M.R., Messing E.M., and Lee, Y.F., E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis, Oncotarget., 2014, vol. 5, no. 23, pp. 12097–12110. https://doi.org/10.18632/oncotarget.2503

    Article  PubMed  PubMed Central  Google Scholar 

  15. Steegmaier, M., Borges, E., Berger, J., Schwarz, H., and Vestweber, D.J., The E-selectin-ligand ESL-1 is located in the Golgi as well as on microvilli on the cell surface, Cell Sci.,1997, vol. 110, no. 6, pp. 687–694.

    CAS  Google Scholar 

  16. Ahn, J., Febbraio, M., and Silverstein, R.L., A novel isoform of human Golgi complex-localized glycoprotein-1 (also known as E-selectin ligand-1, MG-160 and cysteine-rich fibroblast growth factor receptor) targets differential subcellular localization, J. Cell Sci., 2005, vol. 118, pp. 1725–1731. https://doi.org/10.1242/jcs.02310

    Article  CAS  PubMed  Google Scholar 

  17. Steegmaier, M., Levinovitz, A., Isenmann, S., Borges, E., Lenter, M., Kocher, H.P., Kleuser, B., and Vestweber, D., The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor, Nature, 1995, vol. 16, no. 373 (6515), pp. 615–620. https://doi.org/10.1038/373615a0

    Article  Google Scholar 

  18. Miyaoka, Y., Kato, H., Ebato, K., Saito, S., Miyata, N., Imamura, T., and Miyajima, A., Retention in the Golgi apparatus and expression on the cell surface of Cfr/Esl-1/ Glg-1/MG-160 are regulated by two distinct mechanisms, Biochem. J., 2011, vol. 15, no. 440 (1), pp. 33–41. https://doi.org/10.1042/BJ20110318

    Article  CAS  Google Scholar 

  19. Treng, Y.T., Li, W., Chen, C.H., Zhang, S., Chen, J.W., Zhou, X.Z., and Liu, C.C., IIIDB: a database for isoform-isoform interactions and isoform network modules, BMC Genomics, 2015, vol. 16 (suppl 2), p. S10.https://doi.org/10.1186/1471-2164-16-S2-S10

    Article  Google Scholar 

  20. Dunn, K., Kamocka, I., and McDonalc, J., Apractical guide to evaluating colocalization in biological microscopy, Cell Physiol., 2011, vol. 300, no. 4, pp. 723–742. https://doi.org/10.1152/ajpcell.00462.2010

    Article  CAS  Google Scholar 

  21. Zinchuk, V., Zinchuk, O., and Okada, T., Quantitative colocalization analysis of multicolor confocal immunofluorescence microscopy images: pushing pixels to explore biological phenomena, Acta Histochem. Cytochem., 2007, vol. 40, pp. 101–111. https://doi.org/10.1267/ahc.07002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McDonald, J. and Dunn, K., Statistical tests for measures of colocalization in biological microscopy, J. Microscopy, 2013, vol. 255, no. 3, pp. 295–302. https://doi.org/10.1111/jmi.12093

    Article  CAS  Google Scholar 

  23. Wadleigh, M., Daniel, J., and DeAngelo, JamesD., Griffin and Richard, M., After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies, Blood, 2005, vol. 105, pp. 22–30. https://doi.org/10.1182/blood-2003-11-3896

    Article  CAS  PubMed  Google Scholar 

  24. Antonenko, S.V., Gurianov, D.S., and Telegeev, G.D., Colocalization of USP1 and PH domain of Bcr-Abl oncoprotein in terms of chronic myeloid leukemia cell rearrangements, Cytol. Genets, 2016, vol. 50, no. 5, pp. 352–356. https://doi.org/10.3103/s009-5452716050029

    Article  Google Scholar 

  25. Gurianov, D.S., Antonenko, S.V., and Telegeev, G.D., Colocalization of cortactin and PH domain of BCR in HEK293T cells and its potential role in cell signaling, Biopolym. Cell, 2016, vol. 32, no. 1, pp. 26–33. https://doi.org/10.7124/bc.000909

    Article  Google Scholar 

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Authors and Affiliations

  1. Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine

    S. V. Antonenko, I. V. Kravchuk & G. D. Telegeev

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  1. S. V. Antonenko
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  2. I. V. Kravchuk
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  3. G. D. Telegeev
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Correspondence to S. V. Antonenko.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by N. Tarasyuk

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Antonenko, S.V., Kravchuk, I.V. & Telegeev, G.D. Interaction of Bcl-Abl Oncoprotein with the Glg1 Protein in K562 Cells: its Role in the Pathogenesis of Chronic Myeloid Leukemia. Cytol. Genet. 54, 48–54 (2020). https://doi.org/10.3103/S0095452720010028

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