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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
13:56

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions

Published on: July 18, 2013

The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42

A W Oliver1, X He, K Borthwick

  • 1University of Manchester Gynaecological Oncology Laboratories, School of Cancer and Enabling Sciences, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK.

British Journal of Cancer
|December 9, 2010
PubMed
Abstract

Insights

Human papillomavirus type 16 E6 protein, Tax-interacting-protein 1 (Tip-1), and a novel Guanine nucleotide exchange factor (GEF) called ARHGEF16 may cooperate to activate Cdc42. This finding suggests a link between HPV16 E6 and Cdc42 activation in cancer progression.

Area of Science:

  • Molecular biology
  • Cell biology
  • Virology

Background:

  • Guanidine exchange factor (GEF)-catalyzed activation of Rho proteins, including Cdc42, is implicated in cellular transformation and cancer.
  • The human papillomavirus type 16 (HPV16) E6 oncoprotein interacts with Tax-interacting-protein 1 (Tip-1).

Purpose of the Study:

  • To identify and functionally analyze novel Tip-1 binding partners.
  • To investigate the role of a novel Tip-1 binding GEF in Cdc42 activation in the context of HPV16 E6 expression.

Main Methods:

  • Yeast two-hybrid assays and co-immunoprecipitation to identify protein interactions.
  • In vitro kinetic analyses and cell-based assays to measure Rho protein activation.
  • siRNA gene silencing to assess the functional significance of identified proteins.

Main Results:

  • ARHGEF16 was identified as a novel Tip-1 binding protein via its PDZ binding motif.
  • ARHGEF16 levels and Cdc42 activation were increased in cells expressing HPV16 E6.
  • Recombinant ARHGEF16 activated Cdc42, an effect enhanced by Tip-1 and E6; silencing Tip-1 or ARHGEF16 reduced Cdc42 activation in HPV16 E6-expressing cells.

Conclusions:

  • HPV16 E6, Tip-1, and ARHGEF16 cooperate in the activation of Cdc42.
  • These findings suggest a mechanistic link between HPV16 E6 expression and elevated Cdc42 activity, potentially contributing to oncogenesis.

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