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. 1995 Sep;15(9):5188–5195. doi: 10.1128/mcb.15.9.5188

The N-terminal domain of c-Myc associates with alpha-tubulin and microtubules in vivo and in vitro.

N Alexandrova 1, J Niklinski 1, V Bliskovsky 1, G A Otterson 1, M Blake 1, F J Kaye 1, M Zajac-Kaye 1
PMCID: PMC230766  PMID: 7651436

Abstract

The polymerization of alpha- and beta-tubulin into microtubules results in a complex network of microfibrils that have important structural and functional roles in all eukaryotic cells. In addition, microtubules can interact with a diverse family of polypeptides which are believed to directly promote the assembly of microtubules and to modulate their functional activity. We have demonstrated that the c-Myc oncoprotein interacts in vivo and in vitro with alpha-tubulin and with polymerized microtubules and have defined the binding site to the N-terminal region within the transactivation domain of c-Myc. In addition, we have shown that c-Myc colocalizes with microtubules and remains tightly bound to the microtubule network after detergent extraction of intact cells. These findings suggest a potential role for Myc-tubulin interaction in vivo.

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Selected References

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  1. Alfa C. E., Ducommun B., Beach D., Hyams J. S. Distinct nuclear and spindle pole body population of cyclin-cdc2 in fission yeast. Nature. 1990 Oct 18;347(6294):680–682. doi: 10.1038/347680a0. [DOI] [PubMed] [Google Scholar]
  2. Amizuka N., Ozawa H. Intracellular localization and translocation of 1 alpha, 25-dihydroxyvitamin D3 receptor in osteoblasts. Arch Histol Cytol. 1992 Mar;55(1):77–88. doi: 10.1679/aohc.55.77. [DOI] [PubMed] [Google Scholar]
  3. Bhatia K., Huppi K., Spangler G., Siwarski D., Iyer R., Magrath I. Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas. Nat Genet. 1993 Sep;5(1):56–61. doi: 10.1038/ng0993-56. [DOI] [PubMed] [Google Scholar]
  4. Blackwood E. M., Eisenman R. N. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. doi: 10.1126/science.2006410. [DOI] [PubMed] [Google Scholar]
  5. Blackwood E. M., Kretzner L., Eisenman R. N. Myc and Max function as a nucleoprotein complex. Curr Opin Genet Dev. 1992 Apr;2(2):227–235. doi: 10.1016/s0959-437x(05)80278-3. [DOI] [PubMed] [Google Scholar]
  6. Bollag G., McCormick F., Clark R. Characterization of full-length neurofibromin: tubulin inhibits Ras GAP activity. EMBO J. 1993 May;12(5):1923–1927. doi: 10.1002/j.1460-2075.1993.tb05841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brockman J. L., Gross S. D., Sussman M. R., Anderson R. A. Cell cycle-dependent localization of casein kinase I to mitotic spindles. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9454–9458. doi: 10.1073/pnas.89.20.9454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Craig R. W., Buchan H. L., Civin C. I., Kastan M. B. Altered cytoplasmic/nuclear distribution of the c-myc protein in differentiating ML-1 human myeloid leukemia cells. Cell Growth Differ. 1993 May;4(5):349–357. [PubMed] [Google Scholar]
  9. Eisenman R. N., Tachibana C. Y., Abrams H. D., Hann S. R. V-myc- and c-myc-encoded proteins are associated with the nuclear matrix. Mol Cell Biol. 1985 Jan;5(1):114–126. doi: 10.1128/mcb.5.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evan G. I., Lewis G. K., Ramsay G., Bishop J. M. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. doi: 10.1128/mcb.5.12.3610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gu W., Bhatia K., Magrath I. T., Dang C. V., Dalla-Favera R. Binding and suppression of the Myc transcriptional activation domain by p107. Science. 1994 Apr 8;264(5156):251–254. doi: 10.1126/science.8146655. [DOI] [PubMed] [Google Scholar]
  12. Gupta S., Seth A., Davis R. J. Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3216–3220. doi: 10.1073/pnas.90.8.3216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gusse M., Ghysdael J., Evan G., Soussi T., Méchali M. Translocation of a store of maternal cytoplasmic c-myc protein into nuclei during early development. Mol Cell Biol. 1989 Dec;9(12):5395–5403. doi: 10.1128/mcb.9.12.5395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hann S. R., Abrams H. D., Rohrschneider L. R., Eisenman R. N. Proteins encoded by v-myc and c-myc oncogenes: identification and localization in acute leukemia virus transformants and bursal lymphoma cell lines. Cell. 1983 Oct;34(3):789–798. doi: 10.1016/0092-8674(83)90535-4. [DOI] [PubMed] [Google Scholar]
  15. Henriksson M., Bakardjiev A., Klein G., Lüscher B. Phosphorylation sites mapping in the N-terminal domain of c-myc modulate its transforming potential. Oncogene. 1993 Dec;8(12):3199–3209. [PubMed] [Google Scholar]
  16. Kaelin W. G., Jr, Pallas D. C., DeCaprio J. A., Kaye F. J., Livingston D. M. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 1991 Feb 8;64(3):521–532. doi: 10.1016/0092-8674(91)90236-r. [DOI] [PubMed] [Google Scholar]
  17. Kato G. J., Barrett J., Villa-Garcia M., Dang C. V. An amino-terminal c-myc domain required for neoplastic transformation activates transcription. Mol Cell Biol. 1990 Nov;10(11):5914–5920. doi: 10.1128/mcb.10.11.5914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kato G. J., Dang C. V. Function of the c-Myc oncoprotein. FASEB J. 1992 Sep;6(12):3065–3072. doi: 10.1096/fasebj.6.12.1521738. [DOI] [PubMed] [Google Scholar]
  19. Kato G. J., Lee W. M., Chen L. L., Dang C. V. Max: functional domains and interaction with c-Myc. Genes Dev. 1992 Jan;6(1):81–92. doi: 10.1101/gad.6.1.81. [DOI] [PubMed] [Google Scholar]
  20. Kretzner L., Blackwood E. M., Eisenman R. N. Myc and Max proteins possess distinct transcriptional activities. Nature. 1992 Oct 1;359(6394):426–429. doi: 10.1038/359426a0. [DOI] [PubMed] [Google Scholar]
  21. Maxwell S. A., Ames S. K., Sawai E. T., Decker G. L., Cook R. G., Butel J. S. Simian virus 40 large T antigen and p53 are microtubule-associated proteins in transformed cells. Cell Growth Differ. 1991 Feb;2(2):115–127. [PubMed] [Google Scholar]
  22. Osborn M., Weber K. Immunofluorescence and immunocytochemical procedures with affinity purified antibodies: tubulin-containing structures. Methods Cell Biol. 1982;24:97–132. doi: 10.1016/s0091-679x(08)60650-0. [DOI] [PubMed] [Google Scholar]
  23. Penn L. J., Brooks M. W., Laufer E. M., Littlewood T. D., Morgenstern J. P., Evan G. I., Lee W. M., Land H. Domains of human c-myc protein required for autosuppression and cooperation with ras oncogenes are overlapping. Mol Cell Biol. 1990 Sep;10(9):4961–4966. doi: 10.1128/mcb.10.9.4961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pratt W. B., Sanchez E. R., Bresnick E. H., Meshinchi S., Scherrer L. C., Dalman F. C., Welsh M. J. Interaction of the glucocorticoid receptor with the Mr 90,000 heat shock protein: an evolving model of ligand-mediated receptor transformation and translocation. Cancer Res. 1989 Apr 15;49(8 Suppl):2222s–2229s. [PubMed] [Google Scholar]
  25. Randazzo P. A., Weiss O., Kahn R. A. Preparation of recombinant ADP-ribosylation factor. Methods Enzymol. 1992;219:362–369. doi: 10.1016/0076-6879(92)19036-6. [DOI] [PubMed] [Google Scholar]
  26. Royds J. A., Sharrard R. M., Wagner B., Polacarz S. V. Cellular localisation of c-myc product in human colorectal epithelial neoplasia. J Pathol. 1992 Mar;166(3):225–233. doi: 10.1002/path.1711660304. [DOI] [PubMed] [Google Scholar]
  27. Spencer C. A., Groudine M. Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. [DOI] [PubMed] [Google Scholar]
  28. Stone J., de Lange T., Ramsay G., Jakobovits E., Bishop J. M., Varmus H., Lee W. Definition of regions in human c-myc that are involved in transformation and nuclear localization. Mol Cell Biol. 1987 May;7(5):1697–1709. doi: 10.1128/mcb.7.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vallee R. B. Reversible assembly purification of microtubules without assembly-promoting agents and further purification of tubulin, microtubule-associated proteins, and MAP fragments. Methods Enzymol. 1986;134:89–104. doi: 10.1016/0076-6879(86)34078-3. [DOI] [PubMed] [Google Scholar]
  30. Vriz S., Lemaitre J. M., Leibovici M., Thierry N., Méchali M. Comparative analysis of the intracellular localization of c-Myc, c-Fos, and replicative proteins during cell cycle progression. Mol Cell Biol. 1992 Aug;12(8):3548–3555. doi: 10.1128/mcb.12.8.3548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang N., Yan K., Rasenick M. M. Tubulin binds specifically to the signal-transducing proteins, Gs alpha and Gi alpha 1. J Biol Chem. 1990 Jan 25;265(3):1239–1242. [PubMed] [Google Scholar]
  32. Yano T., Sander C. A., Clark H. M., Dolezal M. V., Jaffe E. S., Raffeld M. Clustered mutations in the second exon of the MYC gene in sporadic Burkitt's lymphoma. Oncogene. 1993 Oct;8(10):2741–2748. [PubMed] [Google Scholar]
  33. Zhou R. P., Oskarsson M., Paules R. S., Schulz N., Cleveland D., Vande Woude G. F. Ability of the c-mos product to associate with and phosphorylate tubulin. Science. 1991 Feb 8;251(4994):671–675. doi: 10.1126/science.1825142. [DOI] [PubMed] [Google Scholar]
  34. Zhou R., Daar I., Ferris D. K., White G., Paules R. S., Vande Woude G. pp39mos is associated with p34cdc2 kinase in c-mosxe-transformed NIH 3T3 cells. Mol Cell Biol. 1992 Aug;12(8):3583–3589. doi: 10.1128/mcb.12.8.3583. [DOI] [PMC free article] [PubMed] [Google Scholar]

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