Mad2 is a key component of the spindle assembly checkpoint (SAC) that delays the onset of anaphase until all kinetochores are attached to the spindle. It binds to Cdc20 and prevents it from promoting destruction of an anaphase inhibitor,
Securin. Previously, we showed that a Mad2-binding
protein, p31(comet), formed a complex with Mad2 upon the completion of spindle attachment. Here, we showed that the overexpression of p31(comet) can abolish the Mad2-dependent SAC that is induced by anti-mitotic drugs, including
nocodazole,
taxol, and
monastrol; these drugs, except
monastrol, cause
aneuploidy in HeLa cells. In the absence of Eg5, which is a target of
monastrol, overexpression of p31(comet) caused premature destruction of
Securin and premature sister chromatid separation, but it did not cause
aneuploidy. These results indicated that Eg5
kinesin function might be required for checkpoint exit and mitotic progression. Moreover, overexpression of p31(comet) led to resistance against apoptosis that was induced by
nocodazole and
taxol in human cells, and
taxol resistance was dependent on the p31(comet)/Mad2
protein expression level ratio of in
cancer cell lines. These results indicated that p31(comet) is an
indicator of resistance to anti-mitotic drugs in
cancer cells.