PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis.
PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis.
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DOI：
10.1038/ncomms12355
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发表时间：
2016-08-05
影响因子：
16.6
通讯作者：
Shen WH
中科院分区：
文献类型：
--
作者：
He J;Zhang Z;Ouyang M;Yang F;Hao H;Lamb KL;Yang J;Yin Y;Shen WH
有丝分裂纺锤体的结构完整性是有效的染色体聚合和准确的染色体分离所必需的，以确保有丝分裂的保真度。肿瘤抑制基因PTEN在维持基因组稳定方面具有多种功能。在这里，我们报告了PTEN在有丝分裂中的重要作用，它通过调节有丝分裂运动中的EG5来调节适当的纺锤体结构和染色体聚集。PTEN缺失会导致中期染色体错位，常常导致灾难性的有丝分裂失败。此外，缺乏PTEN的中期细胞表现出纺锤体几何形状的缺陷，突出表现为纺锤体变短。在有丝分裂过程中，PTEN与EG5结合并共定位。PTEN缺乏导致EG5异常磷酸化，并阻止EG5重新募集到有丝分裂纺锤体，导致纺锤体的解体。这些数据证明了PTEN和EG5在有丝分裂过程中控制有丝分裂纺锤体结构和染色体行为的功能相互作用。我们认为PTEN的功能是平衡有丝分裂的磷酸化，以形成适当的纺锤体和忠实的基因组传递。肿瘤抑制基因PTEN的细胞功能之一是维持基因组的稳定。在这里，作者表明，PTEN缺失导致有丝分裂纺锤体缩短和染色体错位，这是由于EG5异常激活所致。
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. One of the cellular functions of the tumour suppressor PTEN is to maintain genome stability. Here, the authors show that PTEN depletion leads to mitotic spindle shortening and chromosome misalignment due to aberrant EG5 activation.