HPV E6 proteins interact with specific PML isoforms and allow distinctions to be made between different POD structures
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 0950-9232Full text not available from this repository.
Official URL: http://dx.doi.org/10.1038/sj.onc.1207631
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|
|Date:||10 June 2004|
|Number of Pages:||11|
|Page Range:||pp. 4662-4672|
Actions (login required)