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and pRB-family-deficient mouse embryo fibroblasts (Duensing and Munger
2003
).
Further experiments suggested that the ability of HPV-16 E7 to interact with
c-tubulin, a component of the pericentriolar material important for microtubule
nucleation, may play a role in the pRB-independent induction of supernumerary
centrosomes (Nguyen et al.
2007
). Disruption of c-tubulin may play a role in the
regulation of centrosome duplication, and this interaction with HPV-16 E7 which
relies on an intact LXCXE motif may hence contribute to pRB-independent
overduplication induced by HPV-16 E7.
12.14 Conclusion
High-risk HPV oncoproteins have evolved to efficiently disrupt host cell cycle
control on multiple levels in order to promote optimal cellular conditions for viral
genome replication to occur. The collateral damage of this profound dysfunction
of cellular regulation is uncontrolled cellular proliferation, genomic instability,
and carcinogenic progression. Loss of centrosome duplication control is one of the
earliest steps in the development of high-risk HPV-associated malignancies and a
hallmark of several other non-HPV-associated cancers. By utilizing the HPV-16
E7 oncoprotein as a tool, much progress has been made in determining the bio-
logical pathways involved in disruption of centrosome duplication control. These
new insights may be utilized in the future to help develop better preventive and
therapeutic approaches.
References
Acilan C, Potter DM, Saunders WS (2007) DNA repair pathways involved in anaphase bridge
formation. Genes Chromosomes Cancer 46:522-531
Avvakumov N, Torchia J, Mymryk JS (2003) Interaction of the HPV E7 proteins with the pCAF
acetyltransferase. Oncogene 22:3833-3841
Azimzadeh J, Bornens M (2007) Structure and duplication of the centrosome. J Cell Sci
120:2139-2142
Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM (1987) Structural and
transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell
lines. J Virol 61:962-971
Berkhout RJ, Bouwes Bavinck JN, ter Schegget J (2000) Persistence of human papillomavirus
DNA in benign and (pre)malignant skin lesions from renal transplant recipients. J Clin
Microbiol 38:2087-2096
Bernat A, Avvakumov N, Mymryk JS, Banks L (2003) Interaction between the HPV E7
oncoprotein and the transcriptional coactivator p300. Oncogene 22:7871-7881
Bibbo M, Dytch HE, Alenghat E, Bartels PH, Wied GL (1989) DNA ploidy profiles as prognostic
indicators in CIN lesions. Am J Clin Pathol 92:261-265
Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. Translated and
annotated by Henry Harris. J Cell Sci 121(Suppl 1):1-84
