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The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression

Korzeniewski, Nina and Treat, Benjamin and Duensing, Stefan (2011) The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression. Molecular Cancer, 10 (1).

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<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Infection with high-risk human papillomaviruses (HPVs) such as HPV-16 is intimately associated with squamous cell carcinomas (SCCs) of the anogenital tract and a subset of oropharyngeal carcinomas. Such lesions, including pre-invasive precursors, frequently show multipolar mitoses and aneuploidy. The high-risk HPV-16-encoded E7 oncoprotein has been shown to rapidly induce centrosome abnormalities thereby causing the formation of supernumerary mitotic spindle poles and increasing the risk for chromosome missegregation. HPV-16 E7 has been found to rapidly induce centriole overduplication, in part, through the simultaneous formation of more than one daughter centriole at single maternal centrioles (centriole multiplication). The precise molecular mechanism that underlies HPV-16 E7-induced centriole multiplication, however, remains poorly understood.</jats:p> </jats:sec> <jats:sec> <jats:title>Findings</jats:title> <jats:p>Here, we show that human keratinocytes engineered to stably express the HPV-16 E7 oncoprotein exhibit aberrant Polo-like kinase 4 (PLK4) protein expression at maternal centrioles. Real-time quantitative reverse transcriptase (qRT-PCR) analysis of these cells revealed an increase of PLK4 mRNA levels compared to control cells. Importantly, the ability of the HPV-16 E7 oncoprotein to induce centriole multiplication was found to correlate with its ability to activate the PLK4 promoter and to up-regulate PLK4 mRNA.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. Our findings encourage further experiments to test transcriptional inhibitors or small molecules targeting PLK4 to prevent centriole abnormalities, mitotic infidelity and malignant progression in HPV-associated neoplasms and other tumors in which PLK4 regulation is disrupted.</jats:p> </jats:sec>


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Korzeniewski, Nina
Treat, Benjaminbrt16@pitt.eduBRT16
Duensing, Stefan
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: December 2011
Date Type: Publication
Journal or Publication Title: Molecular Cancer
Volume: 10
Number: 1
Publisher: Springer Science and Business Media LLC
DOI or Unique Handle: 10.1186/1476-4598-10-61
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Molecular Virology and Microbiology
Refereed: Yes
Date Deposited: 28 Oct 2016 18:48
Last Modified: 05 Sep 2021 14:55


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