Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a critical role in proper axon guidance and mantainance. It has been reported that β3-tubulin is expressed in a wide variety of tumors. Overexpression of this isotype in clinical samples correlates with tumor aggressiveness, resistance to chemotherapeutic drugs, and poor patient survival. The β3 isotype increases tumor aggressiveness by two distinct mechanisms. Incorporation of this isotype makes microtubule networks hypostable, allowing them to resist the cytotoxic effects of microtubule stabilizing drugs like taxanes or epothilones. Mechanistically, it was found that overexpression of β3-tubulin increases the rate of microtubule detachment from microtubule organizing centers, an activity that is suppressed by drugs such as paclitaxel.
