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Update : 2016/04/06

How cancer cells lose mitotic fidelity

Incorrect attachment of kinetochore microtubules causes chromosome missegregation and is normally corrected through Aurora B-mediated phosphorylation of kinetochore targets. Toru Hirota and his colleagues in the Division of Experimental Pathology found that HP1 is an essential CPC component required for full Aurora B activity and that HP1-modulated CPC function is widely impaired in cancer cells with chromosomal instability (published in Developmental Cell 36: 487-497, 2016)..

More in detail:  Incorrect attachment of kinetochore microtubules is the leading cause of chromosome missegregation in cancers. The highly conserved chromosomal passenger complex (CPC), containing mitotic kinase Aurora B as a catalytic subunit, ensures faithful chromosome segregation through destabilizing incorrect microtubule attachments and promoting bi-orientation of chromosomes on the mitotic spindle. It is unknown whether CPC dysfunction affects chromosome segregation fidelity in cancers and, if so, how. Here we report in the literature below that heterochromatin protein 1 (HP1) is an essential CPC component required for full Aurora B activity. HP1 binding to the CPC becomes particularly important when Aurora B phosphorylates kinetochore targets to eliminate erroneous microtubule-attachments. Remarkably, a reduced proportion of HP1-bound to CPC is widespread in cancers, which causes an impairment in Aurora B activity. These results indicate that HP1 is an essential modulator for CPC function, and identify a molecular basis for chromosome segregation errors in cancer cells

Abe, Y., Sako, K., Takagaki, K., Hirayama, Y., Uchida, K.S., Herman, J.A., DeLuca, J.G., Hirota, T.
HP1-Assisted Aurora B Kinase Activity Prevents Chromosome Segregation Errors.
Dev Cell, 36, 487-497 (2016)

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