Inhibition of Bak-induced apoptosis by HPV-18 E6.
Human papillomavirus (HPV) E6 proteins inhibit apoptosis in both p53-dependent and p53-independent manners. A key point in apoptosis is the regulation provided by the Bcl-2 family; and in differentiating keratinocytes, in which HPV replicates, the Bak protein is highly expressed. We show that HPV-18 E6 will inhibit Bak-induced apoptosis and this is mediated by an interaction between the E6 and Bak proteins resulting in degradation of the Bak protein in vivo. We also show that Bak protein interacts with the ubiquitin ligase, E6AP, and that a mutant of Bak defective in E6AP binding is overexpressed in comparison with wild type. These studies suggest that Bak is probably the first naturally occurring target of E6AP to be identified.
Thomas
M
M
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Banks
L
L
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494772:BAK1 protein, human; C494773:Bak1 protein, mouse; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D044767:Ubiquitin-Protein Ligases; D008025:Ligases