The human papillomavirus E7 oncoprotein functionally interacts with the S4 subunit of the 26 S proteasome.
Human papillomaviruses (HPV) have been etiologically linked to human cervical cancer. More than 90% of cervical cancer tissues express two HPV-encoded oncoproteins E6 and E7. Both E6 and E7 proteins possess transformation activity. and together they cooperate to transform primary human keratinocytes, fibroblasts. and epithelial cells. The transforming activity of E7 is associated with its ability to bind the retinoblastoma tumor suppressor protein (Rb). However, the carboxyl-terminal mutants of E7 are also defective for transformation, suggesting that other cellular targets for E7 might exist. We screened a human placenta cDNA library by yeast two-hybrid assay using HPV 16 E7 as a bait and identified the subunit 4 (S4) ATPase of the 26 S proteasome as a novel E7-binding protein. E7 binds to S4 through the carboxyl-terminal zinc binding motif, and the binding is independent of E7 sequences involved in binding to Rb. The interaction between S4 and E7 can be easily detected by in vitro protein binding assays. Moreover, we found that E7 increases the ATPase activity of S4. A recent study has shown that, in epithelial cells, E7 degrades Rb through the 26 S proteasome pathway. We hypothesize that E7 might target Rb for degradation by 26 S proteasome through its interaction with the subunit 4 of the proteasome.
Berezutskaya
E
E
Department of Biochemistry, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Bagchi
S
S
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins; D012097:Repressor Proteins; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
C068651:E6 protein, Human papillomavirus type 16; D009097:Multienzyme Complexes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C109306:S4 ATPase, proteasome