Interaction of the human papillomavirus type 16 E6 oncoprotein with wild-type and mutant human p53 proteins.
The E6 oncoproteins encoded by the cancer-associated human papillomaviruses (HPVs) can associate with and promote the degradation of wild-type p53 in vitro. To gain further insight into this process, the ability of HPV-16 E6 to complex with and promote the degradation of mutant forms of p53 was studied. A correlation between binding and the targeted degradation of p53 was established. Mutant p53 proteins that bound HPV-16 E6 were targeted for degradation, whereas those that did not complex HPV-16 E6 were not degraded. Since the HPV-16 E6-promoted degradation involves the ubiquitin-dependent proteolysis pathway, specific mutations were made in the amino terminus of p53 to examine whether the E6 targeted degradation involved the N-end rule pathway. No requirement for destabilizing amino acids at the N terminus of p53 was found, nor was evidence found that HPV-16 E6 could provide this determinant in trans, indicating that the N-terminal rule pathway is not involved in the E6-promoted degradation of p53.
Scheffner
M
M
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Takahashi
T
T
Huibregtse
J M
JM
Minna
J D
JD
Howley
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011817:Rabbits; D012097:Repressor Proteins; D012156:Reticulocytes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C068651:E6 protein, Human papillomavirus type 16; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53