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Basic Characteristics of Mutations
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Mutation Site
|
E35A |
|
Mutation Site Sentence
|
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. |
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Mutation Level
|
Amino acid level |
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Mutation Type
|
Nonsynonymous substitution |
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Gene/Protein/Region
|
E7 |
|
Standardized Encoding Gene
|
E7
|
|
Genotype/Subtype
|
HPV16 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
-
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
16800784
|
|
Title
|
The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation
|
|
Author
|
Antonsson A,Payne E,Hengst K,McMillan NA
|
|
Journal
|
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
|
|
Journal Info
|
2006 Jul;26(7):455-61
|
|
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.
|
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Sequence Data
|
-
|
|
|