Journal of Biological Chemistry
Volume 284, Issue 34, 21 August 2009, Pages 23072-23082
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Molecular Basis of Cell and Developmental Biology
PinX1 Is a Novel Microtubule-binding Protein Essential for Accurate Chromosome Segregation*

https://doi.org/10.1074/jbc.M109.001990Get rights and content
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Mitosis is an orchestration of dynamic interactions between spindle microtubules and chromosomes, which is mediated by protein structures that include the kinetochores, and other protein complexes present on chromosomes. PinX1 is a potent telomerase inhibitor in interphase; however, its function in mitosis is not well documented. Here we show that PinX1 is essential for faithful chromosome segregation. Deconvolution microscopic analyses show that PinX1 localizes to nucleoli and telomeres in interphase and relocates to the periphery of chromosomes and the outer plate of the kinetochores in mitosis. Our deletion analyses mapped the kinetochore localization domain of PinX1 to the central region and its chromosome periphery localization domain to the C terminus. Interestingly, the kinetochore localization of PinX1 is dependent on Hec1 and CENP-E. Our biochemical characterization revealed that PinX1 is a novel microtubule-binding protein. Our real time imaging analyses show that suppression of PinX1 by small interference RNA abrogates faithful chromosome segregation and results in anaphase chromatid bridges in mitosis and micronuclei in interphase, suggesting an essential role of PinX1 in chromosome stability. Taken together, the results indicate that PinX1 plays an important role in faithful chromosome segregation in mitosis.

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*

This work was supported, in whole or in part, by National Institutes of Health Grants DK-56292, CA89019, CA92080, and CA118948. This work was also supported by Chinese Academy of Science Grants KSCX1-YW-R65 and KSCX2-YW-H10, Chinese 973 Projects 2002CB713700, 2010CB912103, 2007CB914503, and 2006CB943600, Chinese 863 Project 2006AA02A247, Chinese Natural Science Foundation Grants 30270654, 30070349, 90508002, and 30121001, China National Key Projects for Infectious Disease Grant 2008ZX10002-021, American Cancer Society Grant RPG-99-173-01, a Georgia Cancer Coalition Breast Cancer research grant, and an Atlanta Clinical and Translational Science Award Chemical Biology grant (to X. Y.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.