Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, Chuouku, Kumamoto, Japan.
Oncology. 2012;83(4):210-7. doi: 10.1159/000341360. Epub 2012 Aug 11.
High-risk human papillomaviruses (HPVs) are etiologically linked to human cervical and oral cancers. HPV infection leads to aneuploidy, a numerical chromosomal aberration caused by dysregulation of chromosomal segregation. We found that high-risk HPV18 and HPV58 E7 proteins bind to centromere protein C (CENP-C), a component of the kinetochore that is essential for proper chromosomal segregation. Low-risk HPV4, HPV6, and HPV11 E7s do not bind to CENP-C. The PxDLLCxE sequence in conserved region 2 (CR2) of HPV18 E7 is required for E7 binding to CENP-C. Our results indicate that differences in the ability of high- and low-risk HPV E7s to bind to CENP-C reflect the different oncogenic potentials of high- and low-risk type HPVs.
高危型人乳头瘤病毒（HPV）与人类宫颈癌和口腔癌在病因上有关联。HPV 感染会导致非整倍体，即染色体分离失调导致的染色体数目异常。我们发现，高危型 HPV18 和 HPV58 的 E7 蛋白与着丝粒蛋白 C（CENP-C）结合，CENP-C 是动粒的一个组成部分，对于正确的染色体分离至关重要。低危型 HPV4、HPV6 和 HPV11 的 E7 则不与 CENP-C 结合。HPV18 E7 的保守区 2（CR2）中的 PxDLLCxE 序列是 E7 与 CENP-C 结合所必需的。我们的结果表明，高危型和低危型 HPV E7 结合 CENP-C 的能力差异反映了高危型和低危型 HPV 的不同致癌潜力。
