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    A cyclin-binding motif in human papillomavirus type 18 (HPV18) E1^E4 is necessary for association with CDK–cyclin complexes and G2/M cell cycle arrest of keratinocytes, but is not required for differentiation-dependent viral genome amplification or L1 capsid protein expression

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    Authors
    Knight, Gillian L. cc
    Pugh, Alice G.
    Yates, Emma
    Bell, Ian
    Wilson, Regina
    Moody, Cary A.
    Laimins, Laimonis A.
    Roberts, Sally
    Issue Date
    2013-03-20
    
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    Abstract
    The G2/M arrest function of human papillomavirus (HPV) E4 proteins is hypothesized to be necessary for viral genome amplification. Full-length HPV18 E1^E4 protein is essential for efficient viral genome amplification. Here we identify key determinants within a CDK-bipartite consensus recognition motif in HPV18 E1^E4 that are critical for association with active CDK–cyclin complexes and in vitro phosphorylation at the predicted CDK phosphorylation site (threonine 23). The optimal cyclin-binding sequence (43RRLL46) within this E4 motif is required for G2/M arrest of primary keratinocytes and correlates with cytoplasmic retention of cyclin B1, but not cyclin A. Disruption of this motif in the E4 ORF of HPV18 genomes, and the subsequent generation of stable cell lines in primary keratinocytes revealed that this motif was not essential for viral genome amplification or L1 capsid protein induction. We conclude that the HPV18 E4 G2/M arrest function does not play a role in early vegetative events.
    Citation
    A cyclin-binding motif in human papillomavirus type 18 (HPV18) E1^E4 is necessary for association with CDK–cyclin complexes and G2/M cell cycle arrest of keratinocytes, but is not required for differentiation-dependent viral genome amplification or L1 capsid protein expression 2011, 412 (1):196 Virology
    Journal
    Virology
    URI
    http://hdl.handle.net/10545/274327
    DOI
    10.1016/j.virol.2011.01.007
    Additional Links
    http://linkinghub.elsevier.com/retrieve/pii/S0042682211000122
    Type
    Article
    Description
    Investigation into the effects the HPV E4 protein has in viral life cycle
    ISSN
    00426822
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.virol.2011.01.007
    Scopus Count
    Collections
    Environmental Sustainability Research Centre

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