Wang K, Sturt-Gillespie B, Hittle JC, Macdonald D, Chan GK, Yen TJ, Liu ST

The mitotic checkpoint (or spindle assembly checkpoint) is a fail-safe mechanism to prevent chromosome missegregation by delaying anaphase onset in the presence of defective kinetochore-microtubule attachment. The target of the checkpoint is the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Once all chromosomes are properly attached and bi-oriented at the ...

Read More

metaphase plate, the checkpoint needs to be silenced. Previously we and others have reported that TRIP13 AAA-ATPase binds to the mitotic checkpoint silencing protein p31comet. Here we show that endogenous TRIP13 localizes to kinetochores. TRIP13 knockdown delays metaphase-to-anaphase transition. The delay is caused by prolonged presence of the effector for the checkpoint, the mitotic checkpoint complex (MCC) and its association and inhibition of the APC/C. These results suggest that TRIP13 is a novel mitotic checkpoint silencing protein. The ATPase activity of TRIP13 is essential for its checkpoint function, and interference with TRIP13 abolished p31comet mediated mitotic checkpoint silencing. TRIP13 overexpression is a hallmark of cancer cells with chromosomal instability, particularly in certain breast cancers with poor prognosis. We suggest that premature mitotic checkpoint silencing triggered by TRIP13 overexpression may promote cancer development.

Date: Jul. 10, 2014

View in: Pubmed Google Scholar

166887