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p31(comet) inactivates the chemically induced Mad2-dependent spindle assembly checkpoint and leads to resistance to anti-mitotic drugs.

Abstract
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.
AuthorsToshiyuki Habu, Tomohiro Matsumoto
JournalSpringerPlus (Springerplus) Vol. 2 Pg. 562 ( 2013) ISSN: 2193-1801 [Print] Switzerland
PMID24255856 (Publication Type: Journal Article)

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