Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation

Miranda Thomas; Richard Laura; Karin Hepner; Ernesto Guccione; Charles Sawyers; Laurence Lasky; Lawrence Banks

doi:10.1038/sj.onc.1205668

Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation

Oncogene. 2002 Aug 1;21(33):5088-96. doi: 10.1038/sj.onc.1205668.

Authors

Miranda Thomas¹, Richard Laura, Karin Hepner, Ernesto Guccione, Charles Sawyers, Laurence Lasky, Lawrence Banks

Affiliation

¹ International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy.

PMID: 12140759
DOI: 10.1038/sj.onc.1205668

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Activin Receptors, Type II*
Adaptor Proteins, Signal Transducing
Amino Acid Motifs
Amino Acid Sequence
Blotting, Western
Carrier Proteins / chemistry
Carrier Proteins / metabolism*
Cell Line
Cysteine Endopeptidases / metabolism
DNA Mutational Analysis
DNA-Binding Proteins*
Guanylate Kinases
Humans
Membrane Proteins
Molecular Sequence Data
Multienzyme Complexes / metabolism
Nucleoside-Phosphate Kinase / chemistry
Nucleoside-Phosphate Kinase / metabolism*
Oncogene Proteins, Viral / metabolism*
Papillomaviridae / metabolism*
Proteasome Endopeptidase Complex
Protein Binding
Protein Processing, Post-Translational
Proteins*
Repressor Proteins*
Sequence Homology, Amino Acid
Transfection

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
DNA-Binding Proteins
E6 protein, Human papillomavirus type 16
E6 protein, Human papillomavirus type 18
MAGI3 protein, human
Membrane Proteins
Multienzyme Complexes
Oncogene Proteins, Viral
Proteins
Repressor Proteins
Activin Receptors, Type II
Nucleoside-Phosphate Kinase
Guanylate Kinases
MAGI2 protein, human
Cysteine Endopeptidases
Proteasome Endopeptidase Complex