INCENP–aurora B interactions modulate kinase activity and chromosome passenger complex localization

Abstract

INCENP fine tunes the level of aurora B kinase activity, which in turn correlates with different functional states of the chromosome passenger complex.

SUMOylation modulates the function of Aurora-B kinase

“…We also tested whether Aurora-B kinase activity was important for proper localization of Aurora B in the centromere, by treating GFPAurora-B WT cells with the ZM1 inhibitor. In agreement with previous reports (Ditchfield et al, 2003;Xu et al, 2009), chemical inhibition of Aurora B kinase activity did not perturb localization of Aurora B or INCENP to the centromere, indicating that an active kinase is not required for their centromeric localization (Fig. 5F).…”

The Aurora B Kinase Promotes Inner and Outer Kinetochore Interactions in Budding Yeast

“…However, in contrast to these findings, kinetochore assembly appears intact in the budding yeast ipl1-321 temperature-sensitive mutant (Pinsky et al 2006) as well as in Aurora B depleted/inactivated mammalian cells (e.g., Ditchfield et al 2003;Hauf et al 2003). To reconcile these differences, we propose that a minimal level of Aurora B activity is sufficient to phosphorylate Dsn1 and promote kinetochore assembly, whereas higher activity is required to fulfill its other functions (e.g., error correction, spindle assembly, and cytokinesis) (Norden et al 2006;Xu et al 2009). Consistent with this idea, we previously showed that spindle assembly requires higher levels of Ipl1 kinase activity than other Aurora-dependent functions (Kotwaliwale et al 2007).…”

Aurora kinases and spindle assembly: Variations on a common theme?

“…Hence, INCENP was proposed to function as a rheostat controlling the intensity of AurB activation. 82,83 The importance of this type of regulation can hardly be underestimated given the multifaceted role of AurB and, in particular, its 'surgically-precise' function in correcting kinetochore-MT attachments. 23,38,84,85 In addition, it has been reported that endogenous AurB in egg extract can also be activated by local concentration/clustering.…”

“…It, therefore, appears that AurB activity in cells might be quantitatively controlled both at the level of AurB-INCENP interaction 82,83 and at the level of CPC recruitment to centromeric chromatin and MTs 86,[91][92][93][94] (which, by setting the local AurB concentration, may determine the efficiency of kinase oligomerization). Schematic model of aura and aurB regulation during spindle assembly.…”