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: Yuji Yaginuma, Masafumi Yoshimoto, Ayami Eguchi, Aoi Tokuda, Shoko Takahashi
• Journal: Virus research (Virus Res) Vol. 205 Pg. 27-32 (Jul 02 2015) ISSN: 1872-7492 [Electronic] Netherlands
• PMID: 25997930 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Chromosomal Proteins, Non-Histone
• DNA, Satellite
• DNA-Binding Proteins
• E7 protein, Human papillomavirus type 18
• Oncogene Proteins, Viral
• centromere protein C

Topics

• Centromere (genetics, metabolism)
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• DNA, Satellite (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• HeLa Cells
• Human papillomavirus 18 (genetics, metabolism)
• Humans
• Oncogene Proteins, Viral (genetics, metabolism)
• Papillomavirus Infections (genetics, metabolism, virology)
• Protein Binding