MPS1 is involved in the HPV16-E7-mediated centrosomes amplification

Abstract

Background It has been reported that the oncoprotein E7 from human papillomavirus type 16 (HPV16-E7) can induce the excessive synthesis of centrosomes through the increase in the expression of PLK4, which is a transcriptional target of E2F1. On the other hand, it has been reported that increasing MPS1 protein stability can also generate an excessive synthesis of centrosomes. In this work, we analyzed the possible role of MPS1 in the amplification of centrosomes mediated by HPV16-E7. Results Employing qRT-PCR, Western Blot, and Immunofluorescence techniques, we found that E7 induces an increase in the MPS1 transcript and protein levels in the U2OS cell line, as well as protein stabilization. Besides, we observed that inhibiting the expression of MPS1 in E7 protein-expressing cells leads to a significant reduction in the number of centrosomes. Conclusions These results indicate that the presence of the MPS1 protein is necessary for E7 protein to increase the number of centrosomes, and possible implications are discussed.

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

“…HPV genes can instigate genome instability through multiple mechanisms, including cell cycle modulation, 192 , 193 , 194 , 195 interaction with DNA damage repair pathways that redirect high‐fidelity repair mechanisms to viral episomes rather than the host genome, 196 , 197 induction of DNA‐damaging oxidative stress, and modification of telomere length (which is reviewed in Porter and Marra 198 ). HPV integration into the host genome results from heightened genome instability in HPV‐infected cells.…”