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Down-Regulating CENP-E Activity: For Better or for Worse

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Kinesins and Cancer

Abstract

CENP-E is a kinesin located at the kinetochore that mediates chromosome dynamics throughout mitosis. From one end, the molecule is anchored at the kinetochore, while its N-terminus walks toward the microtubule plus-ends. This participates to bring mono-oriented chromosomes toward the metaphase plate in prometaphase. Besides, CENP-E displays a second binding site in its C-terminus and an extremely long coiled-coil domain in its central section. Those features in combination with its motor activity allows CENP-E the unique ability, for a kinesin, to track both growing and shrinking microtubule ends. This tip-tracking ability contributes to the stabilization of chromosomes attachment when they achieve bi-orientation in metaphase and during their poleward movement in anaphase. CENP-E possess several characteristics that makes it a good target for chemotherapeutic strategies: (i) its enzymatic activity can be inhibited, (ii) its function is essential to cell viability, (iii) its roles are thought to be restricted to mitosis, and (iv) it is overexpressed in various cancers, which could open a therapeutic window. Nevertheless although several CENP-E inhibitors have been developed, whether they display therapeutic efficiency remains to be determined.

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Authors and Affiliations

  1. Université Montpellier, CRBM, 34293, Montpellier, France

    Julien Espeut & Ariane Abrieu

  2. CNRS UMR 5237, 1919 Route de mende, 34293, Montpellier, France

    Julien Espeut & Ariane Abrieu

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  1. Julien Espeut
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  2. Ariane Abrieu
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Correspondence to Ariane Abrieu .

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Editors and Affiliations

  1. Chair, Department of Pharmaceutical and Biological Chemistry School of Pharmacy, University College London, London, United Kingdom

    Frank Kozielski, FSB

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Espeut, J., Abrieu, A. (2015). Down-Regulating CENP-E Activity: For Better or for Worse. In: Kozielski, FSB, F. (eds) Kinesins and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9732-0_6

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