Figure 2.

HR-HPV E6 oncoprotein induces p53 degradation, thus impairing the ability of the cell to promote apoptosis. HR-HPV E7 oncoprotein induces the Rb degradation, promoting S phase entry. The E6 protein blocks the binding of the transcription factor p53 to the promoters of pro-apoptotic genes through its binding with the ubiquitin ligase E6-AP, thus inducing its proteasomal degradation. Additionally, the E6 protein promotes transcriptional activation of the promoter of the catalytic subunit of telomerase enzyme (hTERT) in a myc-dependent manner. This mechanism is induced by the degradation of NFX1-91 mediated by the binding of E6 to E6-AP. The E7 oncoprotein induces the degradation of the retinoblastoma protein (pRb) by binding to the Cullin 2 protein (Cul2), which is part of the E3 ubiquitin ligase complex. Thus, the release of E2F occurs along with the subsequent binding as a transcription factor to the genes that regulate the cell cycle.