Interaction of HPV E6 oncoproteins with specific proteasomal subunits.
The Human Papillomavirus E6 oncoproteins have the capacity to target several of their cellular interacting partners for proteasome mediated degradation, and recent proteomic analyses suggest a close involvement of E6 with the cellular proteasome machinery. In this study we have performed an extensive analysis of the capacity of different E6 oncoproteins to interact with specific proteasome components. We demonstrate that multiple subunits of the proteasome can be bound by different HPV E6 oncoproteins. Furthermore, whilst most of these interactions appear independent of the E6AP ubiquitin ligase, the association of E6 with the major ubiquitin-accepting proteasome subunit, S5a, does require the presence of E6AP. One consequence of the interaction between E6/E6AP and S5a is enhanced ubiquitination of this proteasome subunit. These results suggest a complex interplay between E6 and the proteasome, only some aspects of which are dependent upon the E6AP ubiquitin ligase.
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste, Italy.
Vjekoslav
V
Tomaić
Ketaki
K
Ganti
David
D
Pim
Christina
C
Bauer
Christine
C
Blattner
Lawrence
L
Banks
D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins; D054875:Ubiquitination
D009856:Oncogene Proteins, Viral; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D046988:Proteasome Endopeptidase Complex
E6; E6AP; Human Papillomaviruses; Proteasome; S5a