Further, we found that increased polyubiquitination of TUBB3 was correlated with FOXO3a silencing in 5-FU cross-resistant PacR cancer cells which reflects a strong transcriptional feedback control of TUBB3. The role of the ubiquitin-proteasome system in mt polymerization in cells has been previously described but remains underscored because malfunctioning of this system has been implicated in a variety of diseases [60, 61]. Here, TUBB3 is linked to cancer.