Molecular biology of tubulin: its interaction with drugs and genomic organization

Abstract

Microtubules are ubiquitous cellular structures found in eukaryotic organisms and responsible for a variety of functions. These functions include mitosis, motility, cytoskeletal architecture, intracellular transport and secretion. The major structural component of microtubules is tubulin, a dimeric protein molecule consisting of two similar but nonidentical subunits (α and β) each of about molecular weight 55,000. With the introduction of radioactive colchicine for the first time it has been reported that colchicine binds specifically to tubulin. At this point microtubule research stepped up to a new era linking microtubules with other spindle poisons which are structurally diverse as well as binding at different sites on to the tubulin heterodimer. These antimicrotubular agents have already provided valuable information regarding microtubule-mediated cellular functions and its association and dissociation phenomena. Tubulins appear to be conserved proteins based onin vitro copolymerization and comigration on polyacrylamide gel electrophoretic properties. Further, amino acid sequences of both α and β subunits from a variety of sources also appear to be mostly conserved. The evolutionary conservation of tubulin genes is highly reflected at the nucleic acid level as well. The estimation of the number of genes for tubulin and their organization in a variety of organisms have opened up a new dimension to microtubule and tubulin research. The multigene family for tubulins comprising also pseudogenes is suggestive that more than one gene for each α and β tubulin is functional in the cell. Therefore, it has been speculated that different tubulin gene products contribute to functionally different microtubules at specific stages in cell cycle and cell growth. Heterogeneity in both α and β tubulins has already been established during different stages of development of the cell. Obviously, it reflects that tubulin genes are highly regulated and this regulation might be at the transcriptional and/or translational level. Whatever is the actual control mechanism it appears that cells can detect an enhanced pool of depolymerized subunits and a rapid and specific control in tubulin gene expression at the transcriptional and/or post transcriptional level does occur.