Interestingly, the cell lines which can maintain higher levels of DEDs, such as COS-7, also have documented defects in p53 signaling. Reconstitution of DED expression in the caspase-8 deficient NB7 cells similarly leads to an increase in multi-nucleation. This effect resembles the effect of microtubule-directed agents which disrupt mitotic spindle formation and chromosome segregation. However, these microtubule disrupting agents do not efficiently induce differentiation, suggesting that the DEDs may play additional roles following microtubule binding. Collaborative effect is observed between caspase-8 DEDs and microtubule stabilizing agents, but not microtubule-disrupting drugs. It is likely that this Tectorigenin occurs because microtubule-stabilizing agents act to increase DED association with microtubules. Death Tuberostemonine domain proteins are a large and evolutionarily ancient family. Defined by Tube and Pelle, each domain consists of six peptide helices, with the specific homology placing family members into subfamilies that include the DEDs, the classic death domain proteins, the pyrin domains proteins, and the caspase recruitment domain families. Interactions among these proteins are frequently homotypic or within a subfamily, but interactions between different families, and with unrelated proteins, are unknown. Microtubules have several surface helices with which microtubule-binding proteins interact, as well as cell surface clefts bound by KLD/KID-containing proteins such as kinesins, Tau, and MAP2C. While other DED proteins lack the KLD motif in the turn between helix 4 and 5 of the DED structure, it remains possible that some might still associate with microtubules. For example, at least one death domain protein with a CARD fold, CARD6, interacts with microtubules. It is also possible that DED-mediated effects can influence differentiation or proliferation arrest among cells in which the apoptotic pathway is compromised. For example, it is common for tumor cells to express high levels of anti-apoptotic proteins that interrupt the catalytic cascade, or which otherwise alter the threshold of caspase-8 activation required for apoptosis.