CENP-U cooperates with Hec1 to orchestrate kinetochore-microtubule attachment.

Anhui Laboratory of Cellular Dynamics and Chemical Biology, Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China.
Journal of Biological Chemistry (Impact Factor: 4.6). 11/2010; 286(2):1627-38. DOI: 10.1074/jbc.M110.174946
Source: PubMed

ABSTRACT Mitosis is an orchestration of dynamic interaction between chromosomes and spindle microtubules by which genomic materials are equally distributed into two daughter cells. Previous studies showed that CENP-U is a constitutive centromere component essential for proper chromosome segregation. However, the precise molecular mechanism has remained elusive. Here, we identified CENP-U as a novel interacting partner of Hec1, an evolutionarily conserved kinetochore core component essential for chromosome plasticity. Suppression of CENP-U by shRNA resulted in mitotic defects with an impaired kinetochore-microtubule attachment. Interestingly, CENP-U not only binds microtubules directly but also displays a cooperative microtubule binding activity with Hec1 in vitro. Furthermore, we showed that CENP-U is a substrate of Aurora-B. Importantly, phosphorylation of CENP-U leads to reduced kinetochore-microtubule interaction, which contributes to the error-correcting function of Aurora-B. Taken together, our results indicate that CENP-U is a novel microtubule binding protein and plays an important role in kinetochore-microtubule attachment through its interaction with Hec1.

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