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Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18

S S Lee1, B Glaunsinger, F Mantovani

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

Journal of Virology
|September 23, 2000
PubMed

Insights

Viral oncoproteins from human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) target the MUPP1 protein. Inactivating MUPP1 is crucial for the transforming activity of these viruses, suggesting MUPP1 negatively regulates cell proliferation.

Area of Science:

  • Molecular Virology
  • Oncology
  • Cell Biology

Background:

  • DNA tumor viruses often encode oncoproteins that target common cellular factors.
  • Human adenovirus type 9 (Ad9) E4-ORF1 and high-risk human papillomaviruses (HPV) E6 oncoproteins are major oncogenic determinants.
  • These oncoproteins share a functional PDZ domain-binding motif essential for transforming activity and binding to DLG.

Purpose of the Study:

  • To investigate the interaction of Ad9 E4-ORF1 and HPV-18 E6 oncoproteins with the multi-PDZ domain protein MUPP1.
  • To determine the functional consequences of these interactions on cellular processes.
  • To elucidate the role of MUPP1 in viral oncogenesis.

Main Methods:

  • Analysis of PDZ domain-binding motifs of Ad9 E4-ORF1 and HPV-18 E6.
  • Assessment of binding interactions between viral oncoproteins and MUPP1.
  • Investigation of the cellular localization and stability of MUPP1 upon viral protein expression.
  • Functional assays using mutant viral proteins deficient in MUPP1 binding.

Main Results:

  • The PDZ domain-binding motifs of Ad9 E4-ORF1 and HPV-18 E6 mediate binding to MUPP1.
  • Ad9 E4-ORF1 sequesters MUPP1 in the cytoplasm, while HPV-18 E6 targets MUPP1 for degradation.
  • Mutant viral proteins unable to bind MUPP1 lack these specific cellular activities.
  • MUPP1 is a widely expressed cellular adapter protein involved in signal transduction.

Conclusions:

  • The multi-PDZ domain protein MUPP1 is proposed to negatively regulate cellular proliferation.
  • The transforming activities of Ad9 E4-ORF1 and HPV-18 E6 oncoproteins depend, in part, on their ability to inactivate MUPP1.
  • Targeting MUPP1 represents a common strategy employed by unrelated DNA tumor viruses for oncogenesis.

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