HPV-18 E7 conjugates to c-Myc and mediates its transcriptional activity

Yi Wei Wang, Hung Shu Chang, Ching Hui Lin, Winston C Y Yu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Several reports in the literature have indicated that the E6 not only elevates the level of c-Myc level but that the protein also associates with the Myc complex and activates Myc-responsive genes. There would seem to be a mechanism by which this oncogene can modulate cell proliferation and differentiation. Furthermore, an increase in c-Myc levels has also observed during ectopic expression of HPV E7 alone. Using the yeast two-hybrid system, we further found that the c-Myc interacts and forms a specific complex with HPV-16E7. In this study, we have demonstrated that E7 does indeed interact with c-Myc and a sequential deletion analysis of E7 maps the c-Myc interaction site to the carboxyl-terminal region. We determined two HPV-18 E7 binding sites on c-Myc involving the amino acids regions 1-100 and 367-439. The interaction of the high-risk type HPV E7 with c-Myc can augment c-Myc transactivation activity but this does not occur with low-risk type HPV E7. Deletion within the Cys-X-X-Cys repeat motif at the C-terminus of HPV-18 E7 leads to a lost of association with c-Myc and also abolishes the enhancement of c-Myc's transactivation activity. Furthermore, the interaction of HPV-18 E7 with c-Myc functionally promotes c-Myc's DNA-binding ability. Using the hTERT promoter as a model, enhanced c-Myc binding ability to the hTERT promoter as measured by immunoprecipitation assay was observed and occurred in an E7 dose-dependent manner. Taken together, these results provide significant new insights into the association of c-Myc with E7 and the possible involvement of high-risk E7 in oncogenesis.

Original languageEnglish
Pages (from-to)402-412
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Volume39
Issue number2
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • c-Myc
  • E7
  • Human papillomavirus
  • Telomerase
  • Transactivation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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