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Chromosome Alignment and Segregation Regulated by Ubiquitination of Survivin
- Vong, Queenie P., Cao, Kan, Li, Hoi Y., Iglesias, Pablo A., Zheng, Yixian
- Science 2005 v.310 no.5753 pp. 1499-1504
- binding proteins, chromosome segregation, dissociation, kinetochores, metaphase, microtubules, mitosis, pro-apoptotic proteins, protein degradation, protein-protein interactions, ubiquitin, ubiquitination
- 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 Lys⁴⁸ 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, ubiquitinaton regulates dynamic protein-protein interactions and chromosome segregation independently of protein degradation.