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. 2003 Nov;77(22):12331-5.
doi: 10.1128/jvi.77.22.12331-12335.2003.

Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members

Stefan Duensing  1 , Karl Münger
Affiliations

Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members

Stefan Duensing et al. J Virol. 2003 Nov.

Abstract

The human papillomavirus type 16 (HPV-16) E7 oncoprotein rapidly induces centrosome duplication errors in primary human cells, thereby increasing the propensity for multipolar mitoses, which can lead to chromosome missegregation and aneuploidy. We analyzed a series of HPV-16 E7 mutants and demonstrate that this biological activity of the E7 oncoprotein is mediated by sequences encompassing the core pRB binding site but is independent of its ability to inactivate the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130. In addition, interaction of E7 with the S4 subunit of the 26S proteasome and dysregulation of cdc25A transcription are also dispensable for the induction of centrosome duplication errors. Consistent with these results, expression of HPV-16 E7 induces abnormal centrosome duplication in a cell line that lacks functional pRB and in mouse embryo fibroblasts that are deficient for pRB, p107, and p130. These results demonstrate that the molecular mechanism whereby HPV-16 E7 induces centrosome duplication errors is independent of its ability to inactivate pRB, p107, and p130 or to interact with the S4 proteasome subunit.

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Figures

FIG. 1.
FIG. 1.
(A) Schematic representation of HPV-16 E7 mutants used in this study. CR, conserved region. (B) Visualization of centrioles in U-2 OS cells stably expressing centrin-GFP and transiently transfected with empty vector (left) or HPV-16 E7 (right). Mitochondrial DsRED was used as transfection marker. Nuclei were stained with DAPI. Bar, 10 μm. (C) Immunoblot detection of hemagglutinin-tagged full-length and mutant HPV-16 E7 oncoproteins. The actin immunoblot is shown as a loading control. (D) Quantitation of the proportion of U-2 OS/centrin-GFP cells exhibiting abnormal centriole numbers at 48 h after transfection with either empty vector (neo), wild-type HPV-16 E7 or E7 mutants. Each bar shows the average plus the standard error for at least three independent experiments. (E) Quantitation of the proportion of Saos-2 cells exhibiting abnormal centrosome numbers at 48 h after transfection with either empty vector (neo), wild-type HPV-16 E7, or the HPV-16 E7 ΔD21-C24 mutant. Each bar shows the average plus the standard error for at least three independent experiments. (F) Quantitation of the proportion of TKO MEFs exhibiting abnormal centrosome numbers at 48 h after transfection with either empty vector (neo), wild-type HPV-16 E7, or the HPV-16 E7 ΔD21-C24 mutant. Each bar shows the average plus the standard error for at least three independent experiments.
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