Characterization of Physical Binding between Human Papillomavirus 18 Protein E7 and Centromere Protein C

Abstract

Human papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably cancer of the cervix. In the majority of cases, HPV proteins E6 and E7 are continuously expressed and bind a variety of cellular proteins. The precise mechanism of HPV-induced carcinogenesis has not been fully elucidated; therefore, we attempted to identify the cellular proteins that interact with HPV18 E7 to better understand the function of this important protein. Using yeast 2-hybrid screening, we identified centromere protein C (CENP-C) as one of the proteins that interact with HPV18 E7. CENP-C interacted with E7 from HPV18 but not from HPV11. The CR2 domain of HPV18 E7 and the C-terminal region of CENP-C were found to be involved in the binding of these proteins. CENP-C is a component of the inner kinetochore and plays an essential role in proper chromosome segregation, mitotic checkpoint function, and kinetochore assembly. HPV18 E7–CENP-C binding may therefore impair centromere function, in turn causing cancers. We speculate that altered function of CENP-C as a result of interactions with HPV E7 may be associated with chromosomal abnormalities in HPV18-positive cancers.