Abstract
Microtubules (MTs), highly dynamic structures composed of α- and β-tubulin heterodimers, are involved in cell movement and intracellular traffic and are essential for cell division. Within the cell, MTs are not uniform as they can be composed of different tubulin isotypes that are post-translationally modified and interact with different microtubule-associated proteins (MAPs). These diverse intrinsic factors influence the dynamics of MTs. Extrinsic factors such as microtubule-targeting agents (MTAs) can also affect MT dynamics. MTAs can be divided into two main categories: microtubule-stabilizing agents (MSAs) and microtubule-destabilizing agents (MDAs). Thus, the MT skeleton is an important target for anticancer therapy. This review discusses factors that determine the microtubule dynamics in normal and cancer cells and describes microtubule–MTA interactions, highlighting the importance of tubulin isoform diversity and post-translational modifications in MTA responses and the consequences of such a phenomenon, including drug resistance development.
Highlights
Microtubules (MTs), which are dynamic cytoskeletal components, are hollow-tube filaments usually built up of 13 protofilaments composed of α- and β-tubulin heterodimers connected by noncovalent bonds (Figure 1)
We focus on the factors that determine microtubule dynamics in normal and cancer cells
We describe the microtubule–microtubule-targeting agents (MTAs) interplay, highlighting the significance of the diversity of tubulin isoforms and their post-translational modifications in MTA response, and the consequences of this phenomenon, including the development of drug resistance
Summary
Microtubules (MTs), which are dynamic cytoskeletal components, are hollow-tube filaments usually built up of 13 protofilaments composed of α- and β-tubulin heterodimers connected by noncovalent bonds (Figure 1). Compounds from the second group (microtubuleso-called microtubule-targeting agents (MTAs; known as tubulin-binding agents (TBAs), destabilizing agents (MDAs)) decrease or inhibit mainly longitudinal interactions between microtubule-interfering drugs, anti-microtubule drugs, or microtubule poisons) can influence MT heterodimers at high concentrations, resulting in MT depolymerization and decreased polymer mass. The effect of an individual anti-tubulin/anti-microtubule compound on the polymer mass, stability, binding sites are recognized in the tubulin surface and numerous small molecules or macrocyclic and dynamics of microtubules is very complex. Compounds of the first category (microtubule-stabilizing agents (MSAs)), after binding to the tubulin heterodimer, increase the lateral interactions between heterodimers, which at high compound concentration leads to increased polymerization and stabilization of MTs, resulting in increased polymer mass within the cell. Due to the large number of chemical compounds used in cancer therapies, this paper covers only a narrow range of molecules
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