Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation.
The E6 proteins from the high-risk human papillomavirus (HPV) types have previously been shown to target a number of PDZ domain-containing proteins for proteasome-mediated degradation. These include the hDlg tumour suppressor and the MAGI-1 protein. In this study we show that high-risk HPV E6 proteins also target the related MAGI-2 and MAGI-3 proteins for degradation. Moreover, we show that the interaction is specific to one PDZ domain, and that co-expression of this domain can protect each of the full-length MAGI proteins from E6-mediated degradation. These data provide clear indicators for the potential design of compounds that could specifically inhibit the interaction of oncogenic HPV E6 proteins with an important class of target proteins.
Thomas
Miranda
M
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy.
Laura
Richard
R
Hepner
Karin
K
Guccione
Ernesto
E
Sawyers
Charles
C
Lasky
Laurence
L
Banks
Lawrence
L
D030301:Activin Receptors, Type II; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D051528:Guanylate Kinases; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011506:Proteins; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C496469:MAGI3 protein, human; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009856:Oncogene Proteins, Viral; D011506:Proteins; D012097:Repressor Proteins; D030301:Activin Receptors, Type II; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex