Induction of Mitotic Alterations by the Human Papillomavirus Type 16 E7 Oncoprotein: Mechanistic Studies

Abstract

High-risk human papillomaviruses (HPVs) are causative agents of most cervical cancers and a significant portion of other anogenital tract and oral carcinomas. The major oncogenic activities of HPV16 E6 and E7 oncoproteins are associated with the degradation of the p53 and retinoblastoma tumor suppressors, respectively. E6 also causes increased expression of the catalytic subunit of telomerase, hTERT. In addition, E6 and E7 contribute to carcinogenesis through induction of genomic instability. Accurate chromosome segregation during mitosis is essential for preservation of genomic stability and HPV16 E7 perturbs mitosis in several ways. HPV16 E7 induces the synthesis of supernumerary centrosomes and increases the incidence of multipolar mitoses, which can lead to chromosome missegregation. Moreover, HPV16 E7 expression causes a prometaphase delay, which usually reflects an activation of the mitotic spindle assembly checkpoint (SAC), yet some studies suggested that the SAC is abrogated in HPV16 E7-expressing cells.