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.

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*
  • 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

  • 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