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Delocalization of the Microtubule Motor Dynein from Mitotic Spindles by the Human Papillomavirus E7 Oncoprotein Is Not Sufficient for Induction of Multipolar Mitoses

Nguyen, Christine L., McLaughlin-Drubin, Margaret E., Münger, Karl·2008·Cancer Research

Abstract

Dynein is a minus end–directed microtubule motor that transports numerous cargoes throughout the cell. During mitosis, dynein motor activity is necessary for the positioning of spindle microtubules and has also been implicated in inactivating the spindle assembly checkpoint. Mutations in dynein motor and/or accessory proteins are associated with human disease, including cancer, and the delocalization of dynein from mitotic spindles has been correlated with an increased incidence of multipolar spindle formation in some cancer cells that contain supernumerary centrosomes. The high-risk human papillomavirus type 16 (HPV16) E7 oncoprotein induces centrosome overduplication and has been shown to cause multipolar mitotic spindle formation, a diagnostic hallmark of HPV-associated neoplasias. Here, we show that HPV16 E7 expression leads to an increased population of mitotic cells with dynein delocalized from the mitotic spindle. This function maps to sequences of HPV16 E7 that are distinct from the region necessary for centrosome overduplication. However, contrary to previous reports, we provide evidence that dynein delocalization by HPV16 E7 is neither necessary nor sufficient to cause the formation of multipolar mitoses. [Cancer Res 2008;68(21):8715–22]

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Metadata

Authors
Nguyen, C. L., McLaughlin-Drubin, M. E., & Münger, K.
Affiliations
1Infectious Diseases Division, Channing Laboratories, Brigham and Women's Hospital and
Venue
Cancer Research
Published
2008-10-30
Volume
68
Issue
21
Pages
8715-8722
ISSN
  • 0008-5472
  • 1538-7445
Cited by
21
References
1
Language
en

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