The Ipl1/Aurora Protein Kinase

One of our interests is a key regulator of chromosome segregation in all eukaryotes, the Ipl1/Aurora protein kinase. Because the Aurora kinases are oncogenes and amplified in many tumor types, studies on the budding yeast Ipl1 protein are critical to understanding both chromosome segregation and the maintenance of genomic stability. We recently found that Ipl1 leads to the detachment of mono-oriented microtubules, giving the cell a chance to make proper bioriented attachments to kinetochores (Pinsky, B.A. et al., 2003 and 2006). Ipl1 is also required to activate the spindle checkpoint when there is a defect in kinetochore tension but not attachment and we are currently trying to determine how Ipl1 senses tension defects. We have also discovered 3 additional Ipl1 functions that are likely related to a general role in regulating microtubules. Ipl1 is required for spindle breakdown, spindle positioning and spindle assembly. Because all of the Ipl1 functions are related to a common role in regulating microtubules, we are initiating assays to determine how Ipl1 alters microtubule dynamics and stability in vitro. In addition, we are analyzing the regulation of Ipl1 kinase activity and identifying its substrates to understand how it mediates microtubule destabilization. Finally, we are studying the mechanisms that control the dynamic localization of Ipl1 that is likely related to its ability to carry out numerous functions.