The Bcl2 family of proteins, in particular, Mcl1 and Bcl-xL, have been implicated in the regulation of apoptosis from anti-mitotics in a number of different cancer types and models.11–16 However, how mitotic catastrophe turns on cell death machinery is still largely unknown.17–19 Here we provide evidence that antimitotic therapies activate a death receptor 3 (DR3)-mediated signaling pathway to kill cancer cells. This evidence concerns the gene BCL2L1 and cancer.