Apoptosis

, Volume 8, Issue 5, pp 413–450

Microtubules, microtubule-interfering agents and apoptosis

  • F. Mollinedo
  • C. Gajate
Article

DOI: 10.1023/A:1025513106330

Cite this article as:
Mollinedo, F. & Gajate, C. Apoptosis (2003) 8: 413. doi:10.1023/A:1025513106330

Abstract

Microtubules are dynamic polymers that play crucial roles in a large number of cellular functions. Their pivotal role in mitosis makes them a target for the development of anticancer drugs. Microtubule-damaging agents suppress microtubule dynamics, leading to disruption of the mitotic spindle in dividing cells, cell cycle arrest at M phase, and late apoptosis. A better understanding of the processes coupling microtubule damage to the onset of apoptosis will reveal sites of potential intervention in cancer chemotherapy. Inhibition of microtubule dynamics induces persistent modification of biological processes (M arrest) and signaling pathways (mitotic spindle assembly checkpoint activation, Bcl-2 phosphorylation, c-Jun NH2-terminal kinase activation), which ultimately lead to apoptosis through the accumulation of signals that finally reach the threshold for the onset of apoptosis or through diminishing the threshold for engagement of cell death. Microtubules serve also as scaffolds for signaling molecules that regulate apoptosis, such as Bim and survivin, and their release from microtubules affect the activities of these apoptosis regulators. Thus, sustained modification of signaling routes and changes in the scaffolding properties of microtubules seem to constitute two major processes in the apoptotic response induced by microtubule-interfering agents.

apoptosis cancer chemotherapy microtubules microtubule-interfering agent mitotic spindle signal transduction 

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • F. Mollinedo
    • 1
  • C. Gajate
    • 1
  1. 1.Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del CáncerConsejo Superior de Investigaciones Científicas-Universidad de Salamanca, Campus Miguel de UnamunoSalamancaSpain

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