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. J Virol 2008 Mar;82(5):2493-500
Date
12/28/2007Pubmed ID
18160445Pubmed Central ID
PMC2258903DOI
10.1128/JVI.02188-07Scopus ID
2-s2.0-39749192555 (requires institutional sign-in at Scopus site) 119 CitationsAbstract
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.
Author List
Spanos WC, Hoover A, Harris GF, Wu S, Strand GL, Anderson ME, Klingelhutz AJ, Hendriks W, Bossler AD, Lee JHAuthor
Gerald F. Harris Emeritus Professor in the Orthopaedic Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBinding Sites
Cell Adhesion
Cell Division
Humans
Mice
Neoplasm Invasiveness
Papillomaviridae
Protein Tyrosine Phosphatase, Non-Receptor Type 13
Proto-Oncogene Proteins p21(ras)
