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Figure 4 | Cell Division

Figure 4

From: The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

Figure 4

Model explaining the role of the chromosomal passenger complex/Aurora B in spindle checkpoint function. (A) Treatment with the microtubule destabilising drug nocodazole results in a long checkpoint-dependent mitotic arrest. However, even when all kinetochores are unattached the spindle assembly checkpoint is not capable of inhibiting all APC/C's which might explain why these cells do eventually exit from mitosis (mitotic slippage) [58]. If Aurora B is inactivated in these cells, less APC/C's will be inhibited. Still this is sufficient to allow a mitotic delay, but this delay is significantly shorter than when Aurora B is active [14, 15]. (B) Treatment with the microtubule stabilising agent paclitaxel induces a mitotic arrest with a few unattached kinetochores [35] most likely inhibiting less APC/C's than when all kinetochores are unattached. Yet, this number of inhibited APC/C's is sufficient to sustain a robust checkpoint-dependent arrest. Since the unattached kinetochores are generated under the influence of the chromosomal passenger complex/Aurora B [35], inhibition of Aurora B will now silence both the unattached kinetochore-derived checkpoint signal and the additional amplification signal, resulting in an override of the spindle assembly checkpoint. (C) Expression of a chromosomal passenger complex that lacks the coiled-coil domain of INCENP does not affect the microtubule destabilising activity of Aurora B. In the presence of paclitaxel unattached kinetochores are therefore generated but this does not result in a checkpoint-dependent arrest [35]. We propose that due to the low number of unattached kinetochores that are now inhibiting the APC/C, the spindle checkpoint becomes more dependent on this additional chromosomal passenger complex-generated amplification signal to inhibit a sufficient number of APC/C's that allow a robust mitotic arrest.

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