The PDZ Binding Motif of Human Papillomavirus Type 16 E6 Induces PTPN13 Loss, Which Allows Anchorage-Independent Growth and Synergizes with Ras for Invasive Growth

William C Spanos; Andrew Hoover; George F Harris; Shu Wu; Guinevere L Strand; Mary E Anderson; Aloysius J Klingelhutz; Wiljan Hendriks; Aaron D Bossler; John H Lee

doi:10.1128/JVI.02188-07

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The PDZ Binding Motif of Human Papillomavirus Type 16 E6 Induces PTPN13 Loss, Which Allows Anchorage-Independent Growth and Synergizes with Ras for Invasive Growth

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The PDZ Binding Motif of Human Papillomavirus Type 16 E6 Induces PTPN13 Loss, Which Allows Anchorage-Independent Growth and Synergizes with Ras for Invasive Growth

William C Spanos, Andrew Hoover, George F Harris, Shu Wu, Guinevere L Strand, Mary E Anderson, Aloysius J Klingelhutz, Wiljan Hendriks, Aaron D Bossler and John H Lee

Journal of virology, Vol.82(5), pp.2493-2500

03/2008

DOI: 10.1128/JVI.02188-07

PMCID: PMC2258903

PMID: 18160445

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Abstract

The human papillomavirus (HPV) oncogene E6 has been shown to perform multiple functions (p53 degradation, telomerase activation, etc.) that play a role in oncogenic transformation. Beyond known E6 functions, an undefined mechanism that allows cellular invasion requires the E6 PDZ binding motif (PDZBM). Here, we show that HPV type 16 (HPV16) E6 interacts with and induces loss of a protein tyrosine phosphatase (PTPN13) in a PDZBM-dependent manner. PTPN13 loss induced either by the presence of E6 or by a short hairpin RNA strategy allows for anchorage-independent growth (AIG) and synergy with a known oncogene, Ras v12 , resulting in invasive growth in vivo. Restoring PTPN13 expression reverses AIG in cells lacking PTPN13. A genomic analysis of colorectal carcinoma has identified an association between PTPN13 loss-of-function mutations and aberrant Ras signaling. Our findings support this correlation and provide methods for further evaluation of the mechanisms by which PTPN13 loss/Ras expression leads to invasive growth, the results of which will be important for treatment of HPV-related and non-HPV cancer.

Transformation and Oncogenesis

Details

Title: Subtitle: The PDZ Binding Motif of Human Papillomavirus Type 16 E6 Induces PTPN13 Loss, Which Allows Anchorage-Independent Growth and Synergizes with Ras for Invasive Growth
Creators: William C Spanos - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Andrew Hoover - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
George F Harris - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Shu Wu - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Guinevere L Strand - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Mary E Anderson - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Aloysius J Klingelhutz - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Wiljan Hendriks - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
Aaron D Bossler - Radboud University Department of Cell Biology, Nijmegen, The Netherlands
John H Lee - University of Iowa
Resource Type: Journal article
Publication Details: Journal of virology, Vol.82(5), pp.2493-2500
DOI: 10.1128/JVI.02188-07
PMID: 18160445
PMCID: PMC2258903
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology (ASM)
Language: English
Date published: 03/2008
Academic Unit: Microbiology and Immunology; Pathology; Radiation Oncology; Internal Medicine
Record Identifier: 9984001206902771

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