In the present study, the role of stathmin and its phosphorylation in bortezomib-induced cell death was further investigated by overexpression of the WT stathmin and phosphorylation site-deficient stathmin mutants S16A, S25A or S38A in myeloma cells. Overexpression of WT stathmin significantly increased bortezomib-induced cell death. On the contrary, overexpression of the phosphorylation site-deficient stathmin mutants S16A, S25A and S38A significantly decreased, but did not block, bortezomibinduced cell death. Importantly, increased levels of tubulin polymerization were observed upon bortezomib treatment in cells overexpressing WT or mutant stathmin, but to a lesser extent than parental U266 cells (Fig. 5C, Table 1 ). There are several possible explanations as to why bortezomib-induced cell death is not completely blocked by the stathmin mutants. First, endogenous WT stathmin is still present, and thus the mutant protein has to compete with the WT protein. Second, bortezomib can also modulate the activity of other MT regulatory proteins that may also contribute to the cell death [29] . Furthermore, the MT system is not the only event involved in bortezomib-induced cell death in myeloma cells [22, 31] . This suggests that bortezomibinduced cell death is the result of a concerted series of events.