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Two-way traffic: centrosomes and the cell cycle

Nature Reviews Molecular Cell Biology volume 6, pages 743–748 (2005)Cite this article

Abstract

The well recognized activities of the mammalian centrosome — microtubule nucleation, duplication, and organization of the primary cilium — are under the control of the cell cycle. However, the centrosome is more than just a follower of the cell cycle; it can also be essential for the cell to transit G1 and enter S phase. How the centrosome influences G1 progression is a mystery.

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Figure 1: Diagrammatic representation of the microsurgical operation.
Figure 2: Centrosomal proteins and microtubules in post-mitotic karyoplasts.

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References

  1. Karsenti, E. & Vernos, I. The mitotic spindle: a self-made machine. Science 294, 543–547 (2001).

    Article  CAS  Google Scholar 

  2. Wadsworth, P. & Khodjakov, A. E pluribus unum: towards a universal mechanism for spindle assembly. Trends Cell Biol. 14, 413–419 (2004).

    Article  CAS  Google Scholar 

  3. Hinchcliffe, E. H., Miller, F. J., Cham, M., Khodjakov, A. & Sluder, G. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291, 1547–1550 (2001).

    Article  CAS  Google Scholar 

  4. Khodjakov, A. & Rieder, C. L. Centrosomes enhance the fidelity of cytokinesis in vertebrates and are required for cell cycle progression. J. Cell Biol. 153, 237–242 (2001).

    Article  CAS  Google Scholar 

  5. Piel, M., Nordberg, J., Euteneuer, U. & Bornens, M. Centrosome-dependent exit of cytokinesis in animal cells. Science 291, 1550–1553 (2001).

    Article  CAS  Google Scholar 

  6. Rieder, C. L., Faruki, S. & Khodjakov, A. The centrosome in vertebrates: more than a microtubule-organizing center. Trends Cell Biol. 11, 413–419 (2001).

    Article  CAS  Google Scholar 

  7. Murray, A. W. & Kirschner, M. W. Cyclin synthesis drives the early embryonic cell cycle. Nature 339, 275–280 (1989).

    Article  CAS  Google Scholar 

  8. Sluder, G., Miller, F. J. & Rieder, C. L. Reproductive capacity of sea urchin centrosomes without centrioles. Cell Motil. Cytoskeleton 13, 264–273 (1989).

    Article  CAS  Google Scholar 

  9. Snyder, J. A. & McIntosh, J. R. Initiation and growth of microtubules from mitotic centers in lysed mammalian cells. J. Cell Biol. 67, 744–760 (1975).

    Article  CAS  Google Scholar 

  10. Kuriyama, R. & Borisy, G. G. Microtubule-nucleating activity of centrosomes in Chinese hamster ovary cells is independent of the centriole cycle but coupled to the mitotic cycle. J. Cell Biol. 91, 822–826 (1981).

    Article  CAS  Google Scholar 

  11. Vandre, D. D. & Borisy, G. G. in Mitosis: Molecules and Mechanisms (eds Hyams, J. S. & Brinkley, B. R.) 39–76 (Academic Press, New York, 1989).

    Google Scholar 

  12. Centonze, V. E. & Borisy, G. G. Nucleation of microtubules from mitotic centrosomes is modulated by a phosphorylated epitope. J. Cell Sci. 95, 405–411 (1990).

    CAS  PubMed  Google Scholar 

  13. Vandre, D. D., Feng, Y. & Ding, M. Cell cycle-dependent phosphorylation of centrosomes: localization of phosphopeptide specific antibodies to the centrosome. Microsc. Res. Tech. 49, 458–466 (2000).

    Article  CAS  Google Scholar 

  14. Khodjakov, A. & Rieder, C. L. The sudden recruitment of γ-tubulin to the centrosome at the onset of mitosis and its dynamic exchange throughout the cell cycle, do not require microtubules. J. Cell Biol. 146, 585–596 (1999).

    Article  CAS  Google Scholar 

  15. Young, A., Dictenberg, J. B., Purohit, A., Tuft, R. & Doxsey, S. J. Cytoplasmic dynein-mediated assembly of pericentrin and γ-tubulin onto centrosomes. Mol. Biol. Cell 11, 2047–2056 (2000).

    Article  CAS  Google Scholar 

  16. Sluder, G. in Centrosomes in Development and Disease (ed. Nigg, E.) 167–189 (Wiley-VCH, Weinheim, 2004).

    Google Scholar 

  17. Maniotis, A. & Schliwa, M. Microsurgical removal of centrosomes blocks cell reproduction and centriole generation in BSC-1 cells. Cell 67, 495–504 (1991).

    Article  CAS  Google Scholar 

  18. Vogel, C., Kienitz, A., Hofmann, I., Muller, R. & Bastians, H. Crosstalk of the mitotic spindle assembly checkpoint with p53 to prevent polyploidy. Oncogene 23, 6845–6853 (2004).

    Article  CAS  Google Scholar 

  19. Margolis, R. L., Lohez, O. D. & Andreassen, P. R. G1 tetraploidy checkpoint and the suppression of tumorigenesis. J. Cell. Biochem. 88, 673–683 (2003).

    Article  CAS  Google Scholar 

  20. Uetake, Y. & Sluder, G. Cell cycle progression after cleavage failure: mammalian somatic cells do not possess a 'tetraploidy checkpoint'. J. Cell Biol. 165, 609–615 (2004).

    Article  CAS  Google Scholar 

  21. Dammermann, A. & Merdes, A. Assembly of centrosomal proteins and microtubule organization depends on PCM-1. J. Cell Biol. 159, 255–266 (2002).

    Article  CAS  Google Scholar 

  22. Balczon, R., Simerly, C., Takahashi, D. & Schatten, G. Arrest of cell cycle progression during first interphase in murine zygotes microinjected with anti-PCM-1 antibodies. Cell Motil. Cytoskeleton 52, 183–192 (2002).

    Article  CAS  Google Scholar 

  23. Gromley, A. et al. A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase. J. Cell Biol. 161, 535–545 (2003).

    Article  CAS  Google Scholar 

  24. Keryer, G. et al. Dissociation the centrosomal matrix protein AKAP450 from centrioles impairs centriole duplication and cell cycle progression. Mol. Biol. Cell 14, 2436–2446 (2003).

    Article  CAS  Google Scholar 

  25. Augustin, A. et al. PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression. J. Cell Sci. 116, 1551–1562 (2003).

    Article  CAS  Google Scholar 

  26. Patzke, S. et al. Identification of a novel centrosome/microtubule-associated coiled-coil protein involved in cell-cycle progression and spindle organization. Oncogene 24, 1159–1173 (2005).

    Article  CAS  Google Scholar 

  27. Quintyne, N. J. & Schroer, T. A. Distinct cell cycle-dependent roles for dynactin and dynein at centrosomes. J. Cell Biol. 159, 245–254 (2002).

    Article  CAS  Google Scholar 

  28. Doxsey, S., Zimmerman, W. & Mikule, K. Centrosome control of the cell cycle. Trends Cell Biol. 15, 303–311 (2005).

    Article  CAS  Google Scholar 

  29. Matsumoto, Y. & Maller, J. L. A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry. Science 306, 885–888 (2004).

    Article  CAS  Google Scholar 

  30. Geng, Y. et al. Cyclin E ablation in the mouse. Cell. 114, 431–443 (2003).

    Article  CAS  Google Scholar 

  31. Palazzo, R. E., Vogel, J. M., Schnackenberg, B. J., Hull, D. R. & Wu, L. in Curr. Top. Dev. Biol. (eds Palazzo, R. E. & Schatten, G.) 449–470 (Academic Press, San Diego, 2000).

  32. Doxsey, S. J. Centrosomes as command centres for cellular control. Nature Cell Biol. 3, 105–108 (2001).

    Article  Google Scholar 

  33. Fry, A. & Hames, R. in Centrosomes in Development and Disease (ed. Nigg, E.) 143–166 (Wiley-VCH, Weinheim, 2004).

    Google Scholar 

  34. La Terra, S. et al. The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation. J. Cell Biol. 168, 713–722 (2005).

    Article  CAS  Google Scholar 

  35. Lanni, J. S. & Jacks, T. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol. Cell. Biol. 18, 1055–1064 (1998).

    Article  CAS  Google Scholar 

  36. Casenghi, M. et al. p53-independent apoptosis and p53-dependent block of DNA rereplication following mitotic spindle inhibition in human cells. Exp. Cell Res. 250, 339–350 (1999).

    Article  CAS  Google Scholar 

  37. Ciciarello, M. et al. p53 displacement from centrosomes and p53-mediated G1 arrest following transient inhibition of the mitotic spindle. J. Biol. Chem. 276, 19205–19213 (2001).

    Article  CAS  Google Scholar 

  38. Tritarelli, A. et al. p53 localization at centrosomes during mitosis and postmitotic checkpoint are ATM-dependent and require serine 15 phosphorylation. Mol. Biol. Cell 15, 3751–3757 (2004).

    Article  CAS  Google Scholar 

  39. Kaverina, I., Krylyshkina, O. & Small, J. V. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J. Cell Biol. 146, 1033–1044 (1999).

    Article  CAS  Google Scholar 

  40. Kaverina, I., Rottner, K. & Small, J. V. Targeting, capture, and stabilization of microtubules at early focal adhesions. J. Cell Biol. 142, 181–190 (1998).

    Article  CAS  Google Scholar 

  41. Krylyshkina, O. et al. Nanometer targeting of microtubules to focal adhesions. J. Cell Biol. 161, 853–859 (2003).

    Article  CAS  Google Scholar 

  42. D'Addario, M., Arora, P. D., Ellen, R. P. & McCulloch, C. A. Regulation of tension-induced mechanotranscriptional signals by the microtubule network in fibroblasts. J. Biol. Chem. 278, 53090–53097 (2003).

    Article  CAS  Google Scholar 

  43. Trielli, M. O., Andreassen, P. R., Lacroix, F. B. & Margolis, R. L. Differential taxol-dependent arrest of transformed and nontransformed cells in the G1 phase of the cell cycle, and specific-related mortality of transformed cells. J. Cell Biol. 135, 689–700 (1996).

    Article  CAS  Google Scholar 

  44. Sablina, A. A., Chumakov, P. M., Levine, A. J. & Kopnin, B. P. p53 activation in response to microtubule disruption is mediated by integrin–Erk signaling. Oncogene 20, 899–909 (2001).

    Article  CAS  Google Scholar 

  45. Huang, S., Chen, C. S. & Ingber, D. E. Control of cyclin D1, p27Kip1, and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. Mol. Biol. Cell 9, 3179–3193 (1998).

    Article  CAS  Google Scholar 

  46. Ingber, D. E. Tensegrity II: how structural networks influence cellular information processing networks. J. Cell Sci. 116, 1397–1408 (2003).

    Article  CAS  Google Scholar 

  47. Wheatley, D. N. The Centriole: A Central Enigma of Cell Biology (Elsevier Biomedical Press, Amsterdam, 1982).

    Google Scholar 

  48. Paintrand, M., Moudjou, M., Delacroix, H. & Bornens, M. Centrosome organization and centriole architecture: their sensitivity to divalent cations. J. Struct. Biol. 108, 107–128 (1992).

    Article  CAS  Google Scholar 

  49. Rieder, C. L. & Borisy, G. G. The centrosome cycle in PtK2 cells: Asymmetric distribution and structural changes in the pericentriolar material. Biol. Cell. 44, 117–132 (1982).

    Google Scholar 

  50. Sluder, G. & Rieder, C. L. Centriole number and the reproductive capacity of spindle poles. J. Cell Biol. 100, 887–896 (1985).

    Article  CAS  Google Scholar 

  51. Vorobjev, I. A. & Nadezhdina, E. S. The centrosome and its role in the organization of microtubules. Int. Rev. Cytol. 106, 227–293 (1987).

    Article  CAS  Google Scholar 

  52. Bornens, M., Paintrand, M., Berges, J., Marty, M. C. & Karsenti, E. Structural and chemical characterization of isolated centrosomes. Cell Motil. Cytoskeleton 8, 238–249 (1987).

    Article  CAS  Google Scholar 

  53. Mogensen, M. in Centrosomes in Development and Disease (ed. Nigg, E.) 299–319 (Wiley-VCH, Weinheim, 2004).

    Google Scholar 

  54. Moritz, M., Rice, L. & Agard, D. in Centrosomes in Development and Disease (ed. Nigg, E.) 27–41 (Wiley-VCH, Weinheim, 2004).

    Google Scholar 

  55. Doxsey, S. Re-evaluating centrosome function. Nature Rev. Mol. Cell Biol. 2, 688–698 (2001).

    Article  CAS  Google Scholar 

  56. Lange, B. M. Integration of the centrosome in cell cycle control, stress response and signal transduction pathways. Curr. Opin. Cell Biol. 14, 35–43 (2002).

    Article  CAS  Google Scholar 

  57. Wilkinson, C., Andersen, J., Mann, M. & Nigg, E. in Centrosomes in Development and Disease (ed. Nigg, E.) 125–142 (Wiley-VCH, Weinheim, 2004).

    Google Scholar 

  58. Andersen, J. S. et al. Proteomic characterization of the human centrosome by protein correlation profiling. Nature 426, 570–574 (2003).

    Article  CAS  Google Scholar 

  59. Preble, A. M., Giddings, T. M., Jr & Dutcher, S. K. Basal bodies and centrioles: their function and structure. Curr. Top. Dev. Biol. 49, 207–233 (2000).

    Article  CAS  Google Scholar 

  60. Bornens, M. Centrosome composition and microtubule anchoring mechanisms. Curr. Opin. Cell Biol. 14, 25–34 (2002).

    Article  CAS  Google Scholar 

  61. Piel, M., Meyer, P., Khodjakov, A., Rieder, C. L. & Bornens, M. The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317–330 (2000).

    Article  CAS  Google Scholar 

  62. Pelletier, L. et al. The Caenorhabditis elegans centrosomal protein SPD-2 is required for both pericentriolar material recruitment and centriole duplication. Curr. Biol. 14, 863–73 (2004).

    Article  CAS  Google Scholar 

  63. Massague, J. G1 cell-cycle control and cancer. Nature 432, 298–306 (2004).

    Article  CAS  Google Scholar 

  64. Kastan, M. B. & Bartek, J. Cell-cycle checkpoints and cancer. Nature 432, 316–323 (2004).

    Article  CAS  Google Scholar 

  65. Ding, Q. et al. p27Kip1 and cyclin D1 are necessary for focal adhesion kinase (FAK) regulation of cell cycle progression in glioblastoma cells propagated in vitro and in vivo in the scid mouse brain. J. Biol. Chem. 280, 6802–6815 (2005).

    Article  CAS  Google Scholar 

  66. Lowe, S. W., Cepero, E. & Evan, G. Intrinsic tumour suppression. Nature 432, 307–315 (2004).

    Article  CAS  Google Scholar 

  67. Sherr, C. J. & McCormick, F. The RB and p53 pathways in cancer. Cancer Cell 2, 103–112 (2002).

    Article  CAS  Google Scholar 

  68. Bode, A. M. & Dong, Z. Post-translational modification of p53 in tumorigenesis. Nature Rev. Cancer 4, 793–805 (2004).

    Article  CAS  Google Scholar 

  69. Sherr, C. J. & Roberts, J. M. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 18, 2699–2711 (2004).

    Article  CAS  Google Scholar 

  70. Sluder, G. Double or nothing. Curr. Biol. 2, 243–245 (1992).

    Article  CAS  Google Scholar 

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Acknowledgements

I thank S. Doxsey, A. Khodjakov, A. Krzywicka, J. Nordberg and Y. Uetake for helpful discussions. C. English provided invaluable help in the preparation of the figures. I apologize to those whose work could not be cited owing to space limitations.

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  1. the Department of Cell Biology, University of Massachusetts Medical School, 377 Plantation Street, Worcester, 01605, Massachusetts, USA

    Greenfield Sluder

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DATABASES

Entrez Gene

cyclin E

Swiss-Prot

CDK2

p21

p53

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Greenfield Sluder's laboratory

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Sluder, G. Two-way traffic: centrosomes and the cell cycle. Nat Rev Mol Cell Biol 6, 743–748 (2005). https://doi.org/10.1038/nrm1712

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