Article

Centrosome overduplication, chromosomal instability, and human papillomavirus oncoproteins.

Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Environmental and Molecular Mutagenesis (impact factor: 3.71). 04/2009; 50(8):741-7. DOI:10.1002/em.20478 pp.741-7
Source: PubMed

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.

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Keywords

aberrant centrosome numbers
 
abnormal centriole biogenesis
 
centriole flowers
 
centrosome duplication cycle
 
concurrent formation
 
cyclin E/CDK2 complexes
 
delineating different pathways
 
E7 oncoprotein
 
E7 oncoproteins
 
functional consequences
 
genuine disruption
 
high-risk human papillomavirus Type 16
 
HPV-16 E7 oncoprotein
 
HPV-16 E7 oncoprotein triggers
 
pathway
 
PLK4
 
Polo-like kinase 4
 
single maternal centrioles
 
underlying molecular circuitry
 
unique tool
 

Anette Duensing