Abstract
Human papillomavirus type 16 (HPV-16) E6 (16E6) binds the E3 ubiquitin ligase E6AP and p53, thereby targeting degradation of p53 (M. Scheffner, B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley, Cell 63:1129-1136, 1990). Here we show that minimal 16E6-binding LXXLL peptides reshape 16E6 to confer p53 interaction and stabilize 16E6 in vivo but that degradation of p53 by 16E6 requires E6AP expression. These experiments establish a general mechanism for how papillomavirus E6 binding to LXXLL peptides reshapes E6 to then act as an adapter molecule.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cell Cycle Proteins
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Cell Line
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Human papillomavirus 16 / metabolism*
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism*
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Oncogene Proteins, Viral / chemistry
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Oncogene Proteins, Viral / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / metabolism*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae / virology
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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases / biosynthesis
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Ubiquitin-Protein Ligases / chemistry
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Ubiquitin-Protein Ligases / metabolism*
Substances
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CDK5RAP3 protein, human
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Cell Cycle Proteins
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E6 protein, Human papillomavirus type 16
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Oncogene Proteins, Viral
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Peptide Fragments
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Repressor Proteins
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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UBE3A protein, human
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Ubiquitin-Protein Ligases