CENP-U cooperates with Hec1 to orchestrate kinetochore-microtubule attachment.
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.
Anhui Laboratory of Cellular Dynamics and Chemical Biology, Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China.
Shasha
S
Hua
Zhikai
Z
Wang
Kai
K
Jiang
Yuejia
Y
Huang
Tarsha
T
Ward
Lingli
L
Zhao
Zhen
Z
Dou
Xuebiao
X
Yao
D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D020090:Chromosome Segregation / Q000502:physiology*; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006657:Histones; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
C485917:CENPU protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D006657:Histones; C120529:NDC80 protein, human; D009687:Nuclear Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases