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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. doi:10.1038/sj.onc.1207631 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 | ||||
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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 |
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Journal or Publication Title: | ONCOGENE | ||||
Publisher: | NATURE PUBLISHING GROUP | ||||
ISSN: | 0950-9232 | ||||
Official Date: | 10 June 2004 | ||||
Dates: |
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Volume: | 23 | ||||
Number: | 27 | ||||
Number of Pages: | 11 | ||||
Page Range: | pp. 4662-4672 | ||||
DOI: | 10.1038/sj.onc.1207631 | ||||
Publication Status: | Published |
Data sourced from Thomson Reuters' Web of Knowledge
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