Human Papillomavirus Type 16 E7 Oncoprotein Can Induce Abnormal Centrosome Duplication through a Mechanism Independent of Inactivation of Retinoblastoma Protein Family Members

Journal of Virology - Tập 77 Số 22 - Trang 12331-12335 - 2003
Stefan Duensing1, Karl Münger2
1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 USA
2Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Tóm tắt

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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Journal of Virology

Tập 77 Số 22

12331-12335

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