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Viral oncoprotein-induced mislocalization of select PDZ proteins disrupts tight junctions and causes polarity defects

Isabel J Latorre1, Michael H Roh, Kristopher K Frese

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

Journal of Cell Science
|September 6, 2005
PubMed

Insights

Adenovirus E4-ORF1 protein disrupts epithelial cell tight junctions and polarity by binding to PDZ proteins. This inactivation of cellular proteins involved in tight junction assembly is linked to cancer development.

Area of Science:

  • Cell Biology
  • Oncology
  • Virology

Background:

  • Human cancer development is linked to impaired epithelial cell tight junctions and apicobasal polarity.
  • Adenovirus E4-ORF1 protein's oncogenic potential correlates with its binding to PDZ proteins, some of which are crucial for tight junctions.

Purpose of the Study:

  • To investigate if adenovirus E4-ORF1 inhibits tight junction formation in epithelial cells.
  • To identify new PDZ protein targets for E4-ORF1 and human papillomavirus type 18 E6 oncoproteins.

Main Methods:

  • Investigated the interaction of E4-ORF1 with PDZ proteins (MUPP1, MAGI-1, ZO-2, SAP97).
  • Identified PATJ as a novel PDZ-protein target for E4-ORF1 and HPV18 E6.
  • Examined the effect of E4-ORF1 on tight junction localization of PATJ and ZO-2 in epithelial cells.

Main Results:

  • E4-ORF1 sequesters PDZ proteins in the cytoplasm, inhibiting tight junction formation.
  • E4-ORF1 blocks the tight junction localization of PATJ and ZO-2, along with their partners.
  • Disruption of the tight junction barrier and apicobasal polarity was observed in epithelial cells.

Conclusions:

  • Adenovirus E4-ORF1 directly links tumorigenic potential to the inactivation of cellular PDZ proteins.
  • This inactivation impairs tight junction assembly and polarity establishment, contributing to cancer development.

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