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  • Original Paper
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Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins

Oncogene volume 19, pages 5270–5280 (2000)Cite this article

Abstract

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.

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Acknowledgements

We are indebted to Guy James (University of Texas Health Sciences Center, San Antonio) for generously providing MAGI-1 reagents. We also thank Bruce Stevenson for providing the canine ZO-2 expression plasmid. BA Glaunsinger and SS Lee were recipients of a Molecular Virology Training Grant (T32 AI07471) and the US Army Breast Cancer Training Grant (DAMD17-94-J4204), respectively. This work was supported by grants from the National Institutes of Health (RO1 CA58541), the American Cancer Society (RPG-97-668-01-VM), and the US Army (DAMD17-97-1-7082) to RT Javier and an Associazione Italiana per la Ricerca sul Cancro grant to L Banks.

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  1. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Britt A Glaunsinger, Siu Sylvia Lee & Ronald Javier

  2. International Center for Genetic Engineering and Biotechnology, Padriciano 99, I-34012, Trieste, Italy

    Miranda Thomas & Lawrence Banks

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  1. Britt A Glaunsinger
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Glaunsinger, B., Lee, S., Thomas, M. et al. Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins. Oncogene 19, 5270–5280 (2000). https://doi.org/10.1038/sj.onc.1203906

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