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

被引：0
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作者：
Jinxue He
Zhong Zhang
Meng Ouyang
Fan Yang
Hongbo Hao
Kristy L. Lamb
Jingyi Yang
Yuxin Yin
Wen H. Shen
机构：
[1] Weill Medical College of Cornell University,Department of Radiation Oncology
[2] Present address: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment,undefined
[3] Tianjin Lung Cancer Institute,undefined
[4] Tianjin Medical University General Hospital,undefined
[5] Tianjin 300052,undefined
[6] China,undefined
[7] Present address: Department of Pathology,undefined
[8] Institute of Systems Biomedicine,undefined
[9] School of Basic Medical Sciences,undefined
[10] Peking University Health Science Center,undefined
[11] Beijing 100191,undefined
[12] China,undefined
来源：
Nature Communications | / 7卷
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摘要：
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.
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