S S Taylor

..We suggest therefore that Bub1 and BubR1 may integrate different 'spindle assembly signals' into a single signal which can then be interpreted by downstream cell cycle regulators...

..A mitotic checkpoint arrests cell cycle progression in response to spindle damage. It now appears that this checkpoint has two separate arms, one that prevents anaphase and a second that prevents cytokinesis and DNA re-replication...

..This article provides a brief historical overview before focusing on some of the outstanding issues and more recent developments in the field...

..Significantly, we show here that expression of an APC mutant in MIN cells reduces the mitotic index following spindle damage to a level observed in CIN cells, suggesting that APC dysfunction may contribute to CIN...

..Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A...

..Centromeres in Bub1-deficient cells also separate prematurely; however, we show that this is a consequence of SAC dysfunction rather than a direct role for Bub1 in protecting centromeric cohesion...

..Here, we turn our attention to GSK-3 - a protein kinase, which in concert with APC, targets beta-catenin for proteolysis - and ask whether GSK-3 is required for accurate chromosome segregation...

..Together these observations provide a new mechanistic insight into a physiological function for separase self-cleavage...

..A major function of Cenp-F, therefore, is to link the Ndel1/Nde1/Lis1/Dynein pathway to kinetochores. Furthermore, our data demonstrate that Ndel1 and Nde1 play distinct roles to ensure chromosome alignment and segregation...

..Because gamma-TuRC inhibition leads to pleiotropic spindle defects, which are well known to activate kinetochore-derived checkpoint signaling, we believe that this conclusion is premature...

..Because small molecule-mediated inhibition of Aurora A and Aurora B yields distinct phenotypes, our observations indicate that the Auroras may present two avenues for anti-cancer drug discovery...

..Surprisingly, however, cohesion is maintained during the early stages of mitosis, indicating the existence of another mechanism that either inhibits separase or protects its substrate during early mitosis...

..Intriguingly, whereas most of the sister-less kinetochores cluster near the spindle poles, some align at the spindle equator, possibly through merotelic or lateral orientations...

..In addition, these observations raise the possibility that the anti-proliferative effects induced by farnesyl transferase inhibitors may be due to inhibition of Cenp-F function and/or turnover...

..Together, these results suggest that by targeting checkpoint proteins to kinetochores, Aurora B couples chromosome alignment with anaphase onset...

..This raises the possibility that, in the absence of Bub1, other mechanisms contribute to spindle checkpoint function...

..We suggest therefore that the initial APC mutation acts as a 'double whammy', destabilising the genome and setting the stage for deregulated proliferation upon loss of the second APC allele...

..This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis...

..This bifurcation in the signalling mechanism may help explain why many tumour cells mount a robust checkpoint response following spindle damage, despite exhibiting chromosome instability...

..We present data supporting a model wherein cell fate is dictated by two competing networks, one involving caspase activation, the other protecting cyclin B1 from degradation...

..Furthermore, because the mechanism underlying the inhibition is different in each case, caution must be taken when interpreting the data...

....

..We propose that a subset of cancer mutations induce APC mitochondrial localization and that APC regulation of Bcl-2 at mitochondria may contribute to tumor cell survival...