Human papillomavirus type 16 E6 protein inhibits DNA fragmentation via interaction with DNA fragmentation factor 40

The E6 oncoprotein of human papillomavirus (HPV) is critical in cervical cancer development. Using the yeast two-hybrid assay, we showed that HPV-16 E6 (16E6) interacts with one of the DNA fragmentation factors (DFFs), DFF40, which mediates DNA degradation during apoptosis. Furthermore, 16E6 interacts with DFF40 through its zinc finger motif 2 and a bridge section linking the two zinc finger motifs. DNA fragmentation assays disclosed that 16E6 binding to DFF40 leads to blockage of DNA cleavage. Our data collectively suggest that suppression of DNA fragmentation through 16E6–DFF40 interaction is a central event promoting tumorigenesis.