title: PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis.
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.
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Jinxue
authors: J
authors: He
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Zhong
authors: Z
authors: Zhang
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Meng
authors: M
authors: Ouyang
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Fan
authors: F
authors: Yang
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Hongbo
authors: H
authors: Hao
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Kristy L
authors: KL
authors: Lamb
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Jingyi
authors: J
authors: Yang
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Yuxin
authors: Y
authors: Yin
authors: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Wen H
authors: WH
authors: Shen
mesh_terms: D000818:Animals; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C470243:KIF11 protein, human; D051059:PTEN Phosphohydrolase; D016547:Kinesins