Microtubule formation
depends both on chaperone-mediated production and assembly of α/β heterodimers
and on microtubule-associated proteins. Production of α and β tubulin
proteins requires assistance from chaperone proteins. The chaperone prefoldin associates with
nascent tubulin polypeptide chains and delivers them to the CCT chaperone. CCT folds them into stable forms, which are
delivered to the tubulin cofactors A and B [47]. CoA and CoB both transfer tubulin monomers to
the CoC/D/E complex, which assembles the monomers into α/β
heterodimers ready for introduction into microtubules. Tubulin reservoirs are held by the
microtubule-associated protein stathmin (green box), which, depending on
phosphorylation, binds to free tubulin and also destabilizes microtubule
polymers. A host of micotubule-associated
proteins (green circles) associate with the microtubule and regulate addition
and removal of heterodimers from both ends of the microtubule; in some cases,
they have been shown to regulate tubulin levels. While MTA therapies like the
taxanes and Vinca alkaloids target
the equilibrium between α/β tubulin heterodimer and the microtubule
polymer, PPARγ inhibitors could be affecting any of the chaperone proteins or
one of the microtubule-associated proteins that is involved in control of
tubulin levels.
