PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis

Jinxue He, Zhong Zhang, Meng Ouyang, Fan Yang, Hongbo Hao, Kristy L. Lamb, Jingyi Yang, Yuxin Yin () and Wen H. Shen ()
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Jinxue He: Weill Medical College of Cornell University
Zhong Zhang: Weill Medical College of Cornell University
Meng Ouyang: Weill Medical College of Cornell University
Fan Yang: Weill Medical College of Cornell University
Hongbo Hao: Weill Medical College of Cornell University
Kristy L. Lamb: Weill Medical College of Cornell University
Jingyi Yang: Weill Medical College of Cornell University
Yuxin Yin: Weill Medical College of Cornell University
Wen H. Shen: Weill Medical College of Cornell University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Architectural integrity of the mitotic spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the mitotic kinesin motor EG5 for proper spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of spindle geometry, manifested prominently by shorter spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the mitotic spindle apparatus, leading to spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling mitotic spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate mitotic phosphorylation for proper spindle formation and faithful genomic transmission.

Date: 2016
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DOI: 10.1038/ncomms12355

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