Cell biology: Chromosome alignment and segregation regulated by ubiquitination of survivin

Proper chromosome segregation requires the attachment of sister kinetochores to microtubules from opposite spindle poles to form bi-oriented chromosomes on the metaphase spindle. The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. We report that a de-ubiquitinating enzyme, hFAM, regulates chromosome alignment and segregation by controlling both the dynamic association of Survivin with centromeres and the proper targeting of Survivin and Aurora B to centromeres. Survivin is ubiquitinated in mitosis through both Lys ⁴⁸ and Lys⁶³ ubiquitin linkages. Lys⁶³ de-ubiquitination mediated by hFAM is required for the dissociation of Survivin from centromeres, whereas Lys⁶³ ubiquitination mediated by the ubiquitin binding protein Ufd1 is required for the association of survivin with centromeres. Thus, ubiquitination regulates dynamic protein-protein interactions and chromosome segregation independently of protein degradation.