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HPV E6 proteins interact with specific PML isoforms and allow distinctions to be made between different POD structures

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UNSPECIFIED. (2004) HPV E6 proteins interact with specific PML isoforms and allow distinctions to be made between different POD structures. ONCOGENE, 23 (27). pp. 4662-4672. ISSN 0950-9232

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Official URL: http://dx.doi.org/10.1038/sj.onc.1207631

Abstract

Mucosal human papillomaviruses (HPVs) are the causative agents of a number of human pathologies, including benign condylomas, as well as of the majority of cervical cancers and their high-grade precursor lesions. Although the viral E6 protein is known to be essential for driving malignant progression of HPV-infected cells, there are still many uncertainties about its mode of action. In this study, we have analysed the intracellular distribution of the E6 oncoproteins from the high-risk HPV-18 and the low-risk HPV-11. We show that both E6 proteins localize within the nucleus in nuclear bodies that are confocal with the promyelocytic leukaemia (PML) protein. Using a panel of different PML isoforms, we demonstrate specific co-localization between the E6 proteins and PML isoforms I-IV, but not with PML isoforms V and VI. We also demonstrate the interaction between E6 and a subset of PML isoforms in vivo. As a consequence of this interaction, the insoluble form of PML IV is destabilized by HPV-18 E6 through a proteasome-dependent pathway. Interestingly, both HPV-11 E6 and HPV-18 E6 can readily overcome PML IV-induced cellular senescence in primary cells. These results show separable functions for different PML isoforms that are specifically targeted by the HPV E6 oncoproteins.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Journal or Publication Title: ONCOGENE
Publisher: NATURE PUBLISHING GROUP
ISSN: 0950-9232
Date: 10 June 2004
Volume: 23
Number: 27
Number of Pages: 11
Page Range: pp. 4662-4672
Identification Number: 10.1038/sj.onc.1207631
Publication Status: Published
URI: http://wrap.warwick.ac.uk/id/eprint/8368

Data sourced from Thomson Reuters' Web of Knowledge

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