The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation

Antonsson, Annika, Payne, Elizabeth, Hengst, Kylie and McMillan, Nigel A. J. (2006) The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation. Journal of Interferon And Cytokine Research, 26 7: 455-461. doi:10.1089/jir.2006.26.455


Author Antonsson, Annika
Payne, Elizabeth
Hengst, Kylie
McMillan, Nigel A. J.
Title The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation
Journal name Journal of Interferon And Cytokine Research   Check publisher's open access policy
ISSN 1079-9907
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1089/jir.2006.26.455
Volume 26
Issue 7
Start page 455
End page 461
Total pages 7
Editor T. A. Hamilton
G. C. Sen
P. M. Marcus
et al.
Place of publication United States
Publisher Mary Ann Liebert Publishers
Language eng
Subject C1
321015 Oncology and Carcinogenesis
730108 Cancer and related disorders
Abstract It is critical that viruses are able to avoid the antiviral activities of interferon (IFN). We have shown previously that the human papillomavirus (HPV) is able to avoid IFN-alpha via interaction of the HPV-16 E7 protein with IFN regulatory factor-9 (IRF-9). Here, we investigated the details of the interaction using HPV-16 E7 peptide mapping to show that IRF-9 binds HPV-16 E7 in a domain encompassing amino acids 25-36. A closer examination of this region indicates this is a novel proline, glutamate, serine, and threonine-rich (PEST) domain, with a PEST score of 8.74. We have also mapped the region of interaction within IRF-9 and found that amino acids 354-393 play an important role in binding to HPV-16 E7. This region of IRF-9 encompasses the IRF association domain (IAD), a region important for protein-protein interaction central to IRF function. Finally, we used alanine-scanning mutagenesis to determine if E7-IRF-9 interaction was important for E7-mediated cellular transformation and found that the HPV-16 E7 mutants Y25A, E26A, S31A, S32A, and E35A, but not L28A and N29A, caused loss of transformation ability. Preliminary data suggest loss of IRF-9 interaction with E7 mutants correlated with transformation. Our work suggests E7- IRF- 9 interaction is important for the transforming ability of HPV-16 E7 and that HPV-16 E7 may interact with other IRF proteins that have IAD domains.
Keyword Biochemistry & Molecular Biology
Cell Biology
Immunology
Adenovirus E1a
Gene-product
Cervical-cancer
E6 Oncoprotein
In-vivo
Phosphorylation
Alpha
Transactivation
Expression
Worldwide
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 18:07:03 EST