Abstract

Chromosomal instability (CIN) and the resultant aneuploid genomic state is a hallmark of cancer. Whether CIN is cause or consequence of cancer has for long been a matter of debate, but evidence is accumulating that it can contribute to tumor progression. Chromosome instability refers to a high rate of chromosome segregation errors during cell division and my lab aims to understand why cancer cells become chromosomally instable. In order to do so it is essential to first comprehend the molecular pathways that ensure error-free chromosome segregation. An essential protein complex required for faithful chromosome segregation is the Chromosomal Passenger Complex (CPC), consisting of Aurora B kinase, INCENP , survivin and borealin. The CPC has a dynamic localization pattern in the dividing cell being present on the inner centromere in (pro)metaphase while moving to the central spindle in anaphase and midbody in telophase. Given its typical localization pattern it is not surprising the CPC regulates both nuclear and cytoplasmic division. During my talk I will discuss how this protein complex ensures error-free segregation of the duplicated chromosomes, and how tumor cells may have found ways to impair CPC function. Moreover, I will show recent data from my lab suggesting that deacetylation of the CPC subunit INCENP is important for CPC translocation from centromeres to central spindle in anaphase.