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Basic Characteristics of Mutations
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Mutation Site
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L50G |
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Mutation Site Sentence
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An HPV-16 E6 mutant (L50G) that binds CBP/p300, but not E6AP, is still capable of down-regulating p53 transcriptional activity. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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E6 |
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Standardized Encoding Gene
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E6
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Genotype/Subtype
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HPV16 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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CREBBP
TP53
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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10400710
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Title
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The human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300
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Author
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Zimmermann H,Degenkolbe R,Bernard HU,O'Connor MJ
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Journal
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Journal of virology
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Journal Info
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1999 Aug;73(8):6209-19
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Abstract
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The transforming proteins of the small DNA tumor viruses, simian virus 40 (SV40), adenovirus, and human papillomavirus (HPV) target a number of identical cellular regulators whose functional abrogation is required for transformation. However, while both adenovirus E1A and SV40 large T transforming properties also depend on the targeting of the transcriptional coactivator CBP/p300, no such interaction has been described for the HPV oncoprotein E6 or E7. Here, we demonstrate that the HPV-16 E6 protein, previously shown to facilitate the degradation of p53 in a complex with E6-associated protein (E6AP), also targets CBP/p300 in an interaction involving the C-terminal zinc finger of E6 and CBP residues 1808 to 1826. Furthermore, this interaction is limited to E6 proteins of high-risk HPVs associated with cervical cancer that have the capacity to repress p53-dependent transcription. An HPV-16 E6 mutant (L50G) that binds CBP/p300, but not E6AP, is still capable of down-regulating p53 transcriptional activity. Thus, HPV E6 proteins possess two distinct mechanisms by which to abrogate p53 function: the repression of p53 transcriptional activity by targeting the p53 coactivator CBP/p300, and the removal of cellular p53 protein through the proteosome degradation pathway.
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Sequence Data
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-
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