E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway
- Unit of Biomedical Research in Cancer, National Cancer Institute (INCan)/Biomedical Research Institute (IIBM), National Autonomous University of Mexico - UNAM, Av. San Fernando No. 22, Col. Seccion XVI, Tlalpan, 14080 Mexico City (Mexico)
- Unit of Biomedical Research in Cancer, National Cancer Institute (INCan)/Biomedical Research Institute (IIBM), National Autonomous University of Mexico -UNAM, Av. San Fernando No. 22, Col. Seccion XVI, Tlalpan, 14080 Mexico City (Mexico)
Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation.
- OSTI ID:
- 21182793
- Journal Information:
- Virology, Vol. 383, Issue 1; Other Information: DOI: 10.1016/j.virol.2008.09.040; PII: S0042-6822(08)00631-4; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
Similar Records
Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma
PTEN silencing enhances neuronal proliferation and differentiation by activating PI3K/Akt/GSK3β pathway in vitro