Interactions of the PDZ-protein MAGI-1 With Adenovirus E4-ORF1 and High-Risk Papillomavirus E6 Oncoproteins

Oncogene. 2000 Nov 2;19(46):5270-80. doi: 10.1038/sj.onc.1203906.


The oncoproteins of small DNA tumor viruses promote tumorigenesis by complexing with cellular factors intimately involved in the control of cell proliferation. The major oncogenic determinants for human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) are the E4-ORF1 and E6 proteins, respectively. These seemingly unrelated viral oncoproteins are similar in that their transforming activities in cells depend, in part, on a carboxyl-terminal PDZ domain-binding motif which mediates interactions with the cellular PDZ-protein DLG. Here we demonstrated that both Ad9 E4-ORF1 and high-risk HPV E6 proteins also bind to the DLG-related PDZ-protein MAGI-1. These interactions resulted in MAGI-1 being aberrantly sequestered in the cytoplasm by the Ad9 E4-ORF1 protein or being targeted for degradation by high-risk HPV E6 proteins. Transformation-defective mutant viral proteins, however, were deficient for these activities. Our findings indicate that MAGI-1 is a member of a select group of cellular PDZ proteins targeted by both adenovirus E4-ORF1 and high-risk HPV E6 proteins and, in addition, suggest that the tumorigenic potentials of these viral oncoproteins depend, in part, on an ability to inhibit the function of MAGI-1 in cells.

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

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Adenovirus E4 Proteins / genetics
  • Adenovirus E4 Proteins / metabolism*
  • Animals
  • Binding Sites
  • Cell Line
  • Cytoplasm / metabolism
  • DNA-Binding Proteins*
  • Fluorescent Antibody Technique
  • Guanylate Kinases
  • Half-Life
  • Mutation / genetics
  • Nucleoside-Phosphate Kinase / chemistry*
  • Nucleoside-Phosphate Kinase / metabolism*
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism*
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Radioimmunoprecipitation Assay
  • Recombinant Fusion Proteins
  • Repressor Proteins*
  • Transfection


  • Adenovirus E4 Proteins
  • DNA-Binding Proteins
  • E4 protein, Adenovirus 9
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases