title: The human papillomavirus18 E7 protein inhibits CENP-C binding to α-satellite DNA.
abstract: Human papillomavirus (HPV) infection leads to aneuploidy, a numerical chromosomal aberration that is caused by dysregulation of chromosomal segregation. We previously found that the E7 proteins of high-risk HPVs, but not of low-risk HPVs, could bind to centromere protein-C (CENP-C). In this study, we first found that CENP-C could bind centromere α-satellite DNAs using ChIP analysis and HA-tagged CENP-C/nuc transfected 293T cells. We then investigated if HA-CENP-C/nuc binding to α-satellite DNAs was affected by the E7 proteins of high- or low-risk HPVs. We found that transfection of the FLAG tagged HPV18 E7 inhibited the binding of HA-CENP-C/nuc to α-satellite DNAs. This finding was confirmed in HeLa S3 cells transfected with siRNA targeted to HPV18 E7 expression. We therefore speculate that altered function of kinetochores as a result of inhibition of CENP-C and α-satellite DNAs binding may be associated with the chromosomal abnormalities observed in HPV18-positive cancers.
authors.affiliation: Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuouku, Kumamoto 862-0976, Japan. Electronic address: yaginuma@kumamoto-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yaginuma
authors.affiliation: Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuouku, Kumamoto 862-0976, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yoshimoto
authors.affiliation: Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuouku, Kumamoto 862-0976, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Eguchi
authors.affiliation: School of Health Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuouku, Kumamoto 862-0976, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Tokuda
authors.affiliation: School of Health Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuouku, Kumamoto 862-0976, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D002503:Centromere / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004276:DNA, Satellite / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; C060905:centromere protein C
keywords: CENP-C; E7; HPV; α-Satellite DNA