Non-human primate papillomavirus E6-mediated p53 degradation reveals ancient evolutionary adaptation of carcinogenic phenotype to host niche
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View abstract on PubMed
Summary
This summary is machine-generated.Macaque papillomaviruses (PVs) show high-risk E6 proteins degrade monkey p53, unlike human PVs. This host-specific degradation, driven by E6 residue 47 and p53 residue 129, offers insights into primate PV evolution and carcinogenicity.
Area Of Science
- Virology
- Oncology
- Evolutionary Biology
Background
- Non-human primates (NHPs) harbor papillomaviruses (PVs) related to human counterparts.
- Limited research exists on the carcinogenic potential of NHP-PVs.
- The E6 oncoprotein of human papillomaviruses (HPVs) is crucial for oncogenesis by degrading the tumor suppressor p53.
Purpose Of The Study
- To investigate the biochemical activity of macaque PV E6 proteins.
- To determine their ability to bind and degrade host p53 proteins.
- To understand the evolutionary basis of PV carcinogenicity and host specificity.
Main Methods
- In vitro cell co-transfection assays were used to screen macaque PV E6 protein activity.
- p53 degradation assays were performed using human and macaque p53.
- Site-directed mutagenesis identified key residues involved in E6-p53 interaction.
Main Results
- Most high-risk macaque PV (α12 clade) E6 proteins effectively degraded monkey p53.
- A host species barrier for E6-mediated p53 degradation was observed between HPV16 and MfPV3, reversible by swapping p53 residue 129.
- Macaque PV E6 residue 47 interacts with p53 residue 129, mediating host-specific degradation.
- Two macaque PV types (MfPV10, MmPV1) inhibited both human and monkey p53 expression.
Conclusions
- High-risk macaque PV E6 proteins possess the biochemical capability for p53 degradation, suggesting an ancient carcinogenic phenotype.
- Host-specific p53 degradation is mediated by specific E6-p53 residue interactions (E6:47, p53:129).
- The evolution of host species barriers in PVs may involve loss-of-function mutations after primate speciation, impacting carcinogenicity.
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