Delocalization of the microtubule motor Dynein from mitotic spindles by the human papillomavirus E7 oncoprotein is not sufficient for induction of multipolar mitoses.
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.
Nguyen
Christine L
CL
Infectious Diseases Division, Channing Laboratories, Brigham and Women's Hospital and Committee on Virology, Harvard Medical School, Boston, Massachusetts 02115, USA.
McLaughlin-Drubin
Margaret E
ME
Münger
Karl
K
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004398:Dyneins / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008677:Metaphase; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D041681:NIH 3T3 Cells; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D008941:Spindle Apparatus / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D004398:Dyneins