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The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-α

Li, Suiyang, Labrecque, Sylvie, Gauzzi, M Cristina, Cuddihy, Andrew R, Wong, Andrew HT, Pellegrini, Sandra, Matlashewski, Gregory J, Koromilas, Antonis E·1999·Oncogene
DOI 10.1038/sj.onc.1202960
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Abstract

We have examined the effects of human papilloma virus (HPV) E6 proteins on interferon (IFN) signaling. Here we show that expression of the 'malignant' HPV-18 E6 in human HT1080 cells results in inhibition of Jak-STAT activation in response to IFN-alpha but not IFN-gamma. This inhibitory effect is not shared by the 'benign' HPV-11 E6. The DNA-binding and transactivation capacities of the transcription factor ISGF3 are diminished in cells expressing HPV-18 E6 after IFN-alpha treatment as a result of decreased tyrosine phosphorylation of Tyk2, STAT2 and STAT1. However, HPV-18 E6 does not affect the induction of tyrosine phosphorylation and DNA-binding of STAT1 by IFN-gamma. In addition, HPV E6 proteins physically interact with Tyk2. This interaction takes place preferably with HPV-18 E6 and to a lesser extent with HPV-11 E6. The E6/Tyk2 interaction requires the JH6-JH7 domains of Tyk2, which are important for Tyk2 binding to the cytoplasmic portion of IFN-alpha receptor 1 (IFNAR1). These findings demonstrate an inhibitory role of HPV-18 E6 in the IFN-alpha-induced Jak-STAT pathway, which may be explained, at least in part, by the ability of E6 to interact with and impair Tyk2 activation.

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Cited by

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Metadata

Authors
Li, S., Labrecque, S., Gauzzi, M. C., Cuddihy, A. R., Wong, A. H., Pellegrini, S., Matlashewski, G. J., & Koromilas, A. E.
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
1999-10-13
Volume
18
Issue
42
Pages
5727-5737
ISSN
  • 0950-9232
  • 1476-5594
DOI
10.1038/sj.onc.1202960
Cited by
245
References
1
Language
en
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CoChat. (2026). Citation check: The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-α. https://app.cochat.ai/papers/10.1038/sj.onc.1202960
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Li, S., Labrecque, S., Gauzzi, M. C., Cuddihy, A. R., Wong, A. H., Pellegrini, S., Matlashewski, G. J., & Koromilas, A. E. (1999). The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-α. Oncogene. https://doi.org/10.1038/sj.onc.1202960