[18] Congenital neurologic syndromes associated with TUBB3 missense mutations demonstrate the critical importance of class III β-tubulin for normal neural development.

These variations in primary structure affect the paclitaxel (a mimic of Nur77) binding domain on βIII-tubulin and may account for the ability of this isotype to confer resistance to Nur77-initiated apoptosis.

Proteomic analysis has revealed that many factors bound to these cysteine residues are involved in the oxidative stress and glucose deprivation response.

[12] This is particularly interesting in light of the fact that class III β-tubulin first appears in the phylogenetic tree when life emerged from the seas and cells were exposed to atmospheric oxygen.

[25] Other pro-survival factors interacting with class III β-tubulin enabling cellular adaptation to oxidative stress include the molecular chaperone HSP70/GRP75.

This site binds basic helix-loop-helix (bHLH) hypoxia induced transcription factors Hif-1α and Hif-2α and is epigenetically modified in cancer cells with constitutive TUBB3 expression.

When HuR is predominantly in the nucleus, a phenomenon typically occurring in low stage carcinomas, miR-200c suppresses class III β-tubulin translation.

[34][35][36][37] Class III β-tubulin is integral component of a pro-survival, cascading molecular pathway which renders cancer cells resistant to apoptosis and enhances their ability to invade local tissues and metastasize.

[14][38][39][40] Class III β-tubulin performs best as a prognostic biomarker when analyzed in the context of an integrated signature including upstream regulators and downstream effectors.