title: Centrosome overduplication, chromosomal instability, and human papillomavirus oncoproteins.
abstract: Centrosome aberrations are a frequent finding in human tumors. However, very little is known about the molecular mechanisms leading to disruption of centrosome duplication control and the functional consequences of aberrant centrosome numbers. The high-risk human papillomavirus Type 16 (HPV-16) E6 and E7 oncoproteins are overexpressed in HPV-associated malignancies of the anogenital tract and have been instrumental in delineating different pathways of centrosome amplification. Whereas the E6 oncoprotein was found to provoke centrosome accumulation, the HPV-16 E7 oncoprotein triggers a genuine disruption of the centrosome duplication cycle. Importantly, the E7 oncoprotein can rapidly cause centrosome overduplication through a pathway that involves the concurrent formation of multiple daughters at single maternal centrioles (centriole flowers). Several lines of evidence suggest that cyclin E/CDK2 complexes and Polo-like kinase 4 (PLK4) are crucial players in this process. These findings underscore that the HPV-16 E7 oncoprotein is a unique tool to dissect normal and abnormal centriole biogenesis and the underlying molecular circuitry.
authors.affiliation: Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. duensing@pitt.edu
authors.forename: Anette
authors.initials: A
authors.lastname: Duensing
authors.forename: Nicole
authors.initials: N
authors.lastname: Spardy
authors.forename: Payel
authors.initials: P
authors.lastname: Chatterjee
authors.forename: Leon
authors.initials: L
authors.lastname: Zheng
authors.forename: Joshua
authors.initials: J
authors.lastname: Parry
authors.forename: Rolando
authors.initials: R
authors.lastname: Cuevas
authors.forename: Nina
authors.initials: N
authors.lastname: Korzeniewski
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing