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Davy, Clare E.; Jackson, Deborah J.; Raj, Kenneth; Peh, Woei Ling; Southern, Shirley A.; Das, Papia; Sorathia, Rina; Laskey, Peter; Middleton, Kate; Nakahara, Tomomi; Wang, Qian; Masterson, Phillip J.; Lambert, Paul F.; Cuthill, Scott; Millar, Jonathan B. A.; Doorbar, John

Human Papillomavirus Type 16 E1 ∧ E4-Induced G 2 Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes

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  • Medientyp: E-Artikel
  • Titel: Human Papillomavirus Type 16 E1 ∧ E4-Induced G 2 Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes
  • Beteiligte: Davy, Clare E.; Jackson, Deborah J.; Raj, Kenneth; Peh, Woei Ling; Southern, Shirley A.; Das, Papia; Sorathia, Rina; Laskey, Peter; Middleton, Kate; Nakahara, Tomomi; Wang, Qian; Masterson, Phillip J.; Lambert, Paul F.; Cuthill, Scott; Millar, Jonathan B. A.; Doorbar, John
  • Erschienen: American Society for Microbiology, 2005
  • Erschienen in: Journal of Virology
  • Sprache: Englisch
  • DOI: 10.1128/jvi.79.7.3998-4011.2005
  • ISSN: 0022-538X; 1098-5514
  • Schlagwörter: Virology ; Insect Science ; Immunology ; Microbiology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>ABSTRACT</jats:title> <jats:p> Human papillomavirus type 16 (HPV16) can cause cervical cancer. Expression of the viral E1 <jats:sup>∧</jats:sup> E4 protein is lost during malignant progression, but in premalignant lesions, E1 <jats:sup>∧</jats:sup> E4 is abundant in cells supporting viral DNA amplification. Expression of 16E1 <jats:sup>∧</jats:sup> E4 in cell culture causes G <jats:sub>2</jats:sub> cell cycle arrest. Here we show that unlike many other G <jats:sub>2</jats:sub> arrest mechanisms, 16E1 <jats:sup>∧</jats:sup> E4 does not inhibit the kinase activity of the Cdk1/cyclin B1 complex. Instead, 16E1 <jats:sup>∧</jats:sup> E4 uses a novel mechanism in which it sequesters Cdk1/cyclin B1 onto the cytokeratin network. This prevents the accumulation of active Cdk1/cyclin B1 complexes in the nucleus and hence prevents mitosis. A mutant 16E1 <jats:sup>∧</jats:sup> E4 (T22A, T23A) which does not bind cyclin B1 or alter its intracellular location fails to induce G <jats:sub>2</jats:sub> arrest. The significance of these results is highlighted by the observation that in lesions induced by HPV16, there is evidence for Cdk1/cyclin B1 activity on the keratins of 16E1 <jats:sup>∧</jats:sup> E4-expressing cells. We hypothesize that E1 <jats:sup>∧</jats:sup> E4-induced G <jats:sub>2</jats:sub> arrest may play a role in creating an environment optimal for viral DNA replication and that loss of E1 <jats:sup>∧</jats:sup> E4 expression may contribute to malignant progression. </jats:p>
  • Zugangsstatus: Freier Zugang