High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation.
Human papillomavirus (HPV) E6 protein can inactivate tumor suppressor p53 by inducing its degradation. We now find that high-risk HPV E6 binds to p53 at two distinct sites; one is within the core structure of p53, and another is at the C terminus of p53. Binding to the core of p53 is required for E6-mediated degradation, as shown by deletion analysis and the properties of a point mutant at residue 135. Both low- and high-risk HPV E6 can bind to a C-terminal region of p53, but these interactions do not induce degradation. These results resolve previous seemingly contradictory findings that attributed the distinctive functional properties of high- and low-risk E6 proteins to either a difference in their abilities to associate with p53 or a difference in their N-terminal structures.
Li
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Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
Coffino
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D001665:Binding Sites; D011232:Chemical Precipitation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000378:metabolism
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase