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    Oncogenic MYC amplifies mitotic perturbations

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    Authors
    Littler, Samantha
    Sloss, O
    Geary, B
    Pierce, A
    Whetton, Anthony D
    Taylor, Stephen S
    Affiliation
    Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Cancer Research Centre, 555 Wilmslow Road, Manchester M20 4GJ, UK
    Issue Date
    2019
    
    Metadata
    Show full item record
    Abstract
    The oncogenic transcription factor MYC modulates vast arrays of genes, thereby influencing numerous biological pathways including biogenesis, metabolism, proliferation, apoptosis and pluripotency. When deregulated, MYC drives genomic instability via several mechanisms including aberrant proliferation, replication stress and ROS production. Deregulated MYC also promotes chromosome instability, but less is known about how MYC influences mitosis. Here, we show that deregulating MYC modulates multiple aspects of mitotic chromosome segregation. Cells overexpressing MYC have altered spindle morphology, take longer to align their chromosomes at metaphase and enter anaphase sooner. When challenged with a variety of anti-mitotic drugs, cells overexpressing MYC display more anomalies, the net effect of which is increased micronuclei, a hallmark of chromosome instability. Proteomic analysis showed that MYC modulates multiple networks predicted to influence mitosis, with the mitotic kinase PLK1 identified as a central hub. In turn, we show that MYC modulates several PLK1-dependent processes, namely mitotic entry, spindle assembly and SAC satisfaction. These observations thus underpin the pervasive nature of oncogenic MYC and provide a mechanistic rationale for MYC's ability to drive chromosome instability.
    Citation
    Littler S, Sloss O, Geary B, Pierce A, Whetton AD, Taylor SS. Oncogenic MYC amplifies mitotic perturbations. Open Biol. 2019 Aug 30;9(8):190136.
    Journal
    Open Biology
    URI
    http://hdl.handle.net/10541/622224
    DOI
    10.1098/rsob.190136
    PubMed ID
    31455158
    Additional Links
    https://dx.doi.org/10.1098/rsob.190136
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1098/rsob.190136
    Scopus Count
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    All Paterson Institute for Cancer Research

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