Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members.
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.
Duensing
Stefan
S
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. stefan_duensing@hms.harvard.edu
Münger
Karl
K
D000818:Animals; D018385:Centrosome / Q000502:physiology*; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D010447:Peptide Hydrolases / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D016160:Retinoblastoma Protein / Q000502:physiology*
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; C059731:oncogene protein E7, Human papillomavirus type 16; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease