人乳头瘤病毒 18 型 E7 蛋白抑制 CENP-C 与α-卫星 DNA 的结合。

The human papillomavirus18 E7 protein inhibits CENP-C binding to α-satellite DNA.

机构信息

Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuouku, Kumamoto 862-0976, Japan.

出版信息

Virus Res. 2015 Jul 2;205:27-32. doi: 10.1016/j.virusres.2015.04.019. Epub 2015 May 18.

DOI:10.1016/j.virusres.2015.04.019

PMID:25997930

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.

摘要

人乳头瘤病毒（HPV）感染导致非整倍体，这是一种由染色体分离失调引起的染色体数目异常。我们之前发现，高危型 HPV 的 E7 蛋白，而不是低危型 HPV 的 E7 蛋白，能够与着丝粒蛋白-C（CENP-C）结合。在这项研究中，我们首先发现 CENP-C 可以通过 ChIP 分析和用 HA 标记的 CENP-C/nuc 转染的 293T 细胞来结合着丝粒α卫星 DNA。然后，我们研究了高危型或低危型 HPV 的 E7 蛋白是否会影响 HA-CENP-C/nuc 与α卫星 DNA 的结合。我们发现，转染 FLAG 标记的 HPV18 E7 抑制了 HA-CENP-C/nuc 与α卫星 DNA 的结合。这一发现在转染靶向 HPV18 E7 表达的 siRNA 的 HeLa S3 细胞中得到了证实。因此，我们推测，由于抑制了 CENP-C 和α卫星 DNA 的结合，动粒功能的改变可能与 HPV18 阳性癌症中观察到的染色体异常有关。