title: 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.
authors.affiliation: Department of Morphological and Functional Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. yaginuma@kumamoto-u.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yaginuma
authors.forename: Kinya
authors.initials: K
authors.lastname: Yoda
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D001921:Brain / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; C060905:centromere protein C