Abstract
Highly conserved α- and β-tubulin heterodimers assemble into dynamic microtubules and perform multiple important cellular functions such as structural support, pathway for transport and force generation in cell division. Tubulin exists in different forms of isotypes expressed by specific genes with spatially- and temporally-regulated expression levels. Some tubulin isotypes are differentially expressed in normal and neoplastic cells, providing a basis for cancer chemotherapy drug development. Moreover, specific tubulin isotypes are overexpressed and localized in the nuclei of cancer cells and/or show bioenergetic functions through the regulation of the permeability of mitochondrial ion channels. It has also become clear that tubulin isotypes are involved in multiple cellular functions without being incorporated into microtubule structures. Understanding the mutations of tubulin isotypes specifically expressed in tumors and their post-translational modifications might help to identify precise molecular targets for the design of novel anti-microtubular drugs. Knowledge of tubulin mutations present in tubulinopathies brings into focus cellular functions of tubulin in brain pathologies such as Alzheimer’s disease. Uncovering signaling pathways which affect tubulin functions during antigen-mediated activation of mast cells presents a major challenge in developing new strategies for the treatment of inflammatory and allergic diseases. γ-tubulin, a conserved member of the eukaryotic tubulin superfamily specialized for microtubule nucleation is a target of cell cycle and stress signaling. Besides its microtubule nucleation role, γ-tubulin functions in nuclear and cell cycle related processes. This special issue “Tubulin: Structure, Functions and Roles in Disease” contains eight articles, five of which are original research papers and three are review papers that cover diverse areas of tubulin biology and functions under normal and pathological conditions.
Highlights
The α and β monomers of tubulin exist as isotypes differing in their amino acid sequence encoded by different genes. α/β heterodimers polymerize into microtubules, which are indispensable for cell division and growth
An increase in microtubule dynamicity has been found in cells which overexpress βIII-tubulin and is likely to be related to the resistance of cancer cells to anti-microtubular drugs [13]. βII-tubulin is commonly expressed in a number of transformed cells and is often found in cell nuclei
Microtubule nucleation from centrosomes is mediated by γ-tubulin complexes, and it has been suggested that protein tyrosine kinases could modulate microtubule nucleation in activated mast cells [27,28,29]
Summary
The α and β monomers of tubulin exist as isotypes differing in their amino acid sequence encoded by different genes. α/β heterodimers polymerize into microtubules, which are indispensable for cell division and growth. The expression of specific isotypes of tubulin is associated with cancer, but the molecular mechanisms behind this effect are still largely unknown. The mutations of tubulin isotypes expressed in invasive tumors affect the binding of anti-cancer drugs and may contribute to drug resistance. Nuclear βII-tubulin is found in aggressive metastatic tumors, and its association with anti-microtubular drugs paclitaxel and vinblastine as well as presence in molecular forms has been suggested [2,3]. 2. Expression of Tubulin Isotypes and Nuclear Localization as a Prognostic Marker of Metastatic Tumors. An increase in microtubule dynamicity has been found in cells which overexpress βIII-tubulin and is likely to be related to the resistance of cancer cells to anti-microtubular drugs [13]. Data on the interactions of γ-tubulin with lamins, nuclear envelopes, and transcription factors suggest these interactions’ roles in nuclei organization and in the regulation of gene expression across various kingdoms [17]
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