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 language | English |
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Pages (from-to) | 402-412 |
Number of pages | 11 |
Journal | International Journal of Biochemistry and Cell Biology |
Volume | 39 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2007 |
Externally published | Yes |
Keywords
- E7
- Human papillomavirus
- Telomerase
- Transactivation
- c-Myc
ASJC Scopus subject areas
- Biochemistry
- Cell Biology