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PTEN Regulates EG5 to Control Spindle Architecture and Chromosome Congression During Mitosis

Overview
Journal Nat Commun
Specialty Biology
Date 2016 Aug 6
PMID 27492783
Citations 31
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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.

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References
1.
Song M, Carracedo A, Salmena L, Song S, Egia A, Malumbres M . Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell. 2011; 144(2):187-99. PMC: 3249980. DOI: 10.1016/j.cell.2010.12.020. View

2.
Ferenz N, Gable A, Wadsworth P . Mitotic functions of kinesin-5. Semin Cell Dev Biol. 2010; 21(3):255-9. PMC: 2844466. DOI: 10.1016/j.semcdb.2010.01.019. View

3.
Sawin K, LeGuellec K, Philippe M, Mitchison T . Mitotic spindle organization by a plus-end-directed microtubule motor. Nature. 1992; 359(6395):540-3. DOI: 10.1038/359540a0. View

4.
Drummond D, Hagan I . Mutations in the bimC box of Cut7 indicate divergence of regulation within the bimC family of kinesin related proteins. J Cell Sci. 1998; 111 ( Pt 7):853-65. DOI: 10.1242/jcs.111.7.853. View

5.
Chalhoub N, Baker S . PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2008; 4:127-50. PMC: 2710138. DOI: 10.1146/annurev.pathol.4.110807.092311. View