A minor beta-tubulin essential for mammalian cell proliferation

Mammals use tubulin from multiple genes to construct microtubules. Some genes are expressed in a tissue specific manner, while others are expressed in almost all cell types. beta5-Tubulin is a minor, ubiquitous isoform whose overexpression was recently shown to disrupt microtubules. Using inhibitory RNA, we now report that suppression of beta5 production in both human and hamster cells blocks cell proliferation. Cells depleted of beta5 either trigger the mitotic checkpoint and undergo apoptosis; or they experience a transient mitotic block, a high incidence of lagging chromosomes, and progression into G1 without cytokinesis to become large, flat cells with elevated DNA content. Microtubules appear to be normally organized in cells depleted of beta5, but they are rich in acetylated alpha-tubulin indicating that they may be more stable than normal. The results provide the first evidence that a specific isoform of beta-tubulin is required for mitosis.