Human papillomavirus 16 E6 protein (HPV16 E6)

The Human papillomavirus 16 E6 protein is a small oncoprotein of approximately 150 amino acids, featuring two zinc-binding domains (E6N and E6C) that enable interactions with host proteins.[1][2][5] It primarily functions by recruiting the ubiquitin ligase E6AP to promote p53 ubiquitination and proteasomal degradation, thereby impairing apoptosis and enabling uncontrolled cell proliferation.[1][2][4][9] E6 also upregulates telomerase reverse transcriptase (hTERT) for cellular immortalization, disrupts cell cycle regulation, inhibits interferon signaling for immune evasion, and targets PDZ domain proteins like MAGI-1 and SAP97 for degradation, contributing to oncogenesis.[1][3][5] These activities are central to the transforming potential of high-risk HPV16, particularly in cervical cancer where E6 expression is invariably maintained.[2][5][9] Structurally, E6 self-associates via its N-terminal domain, a process required for efficient p53 degradation, and its C-terminal PDZ-binding motif ensures specificity in targeting tumor suppressors.[2][3][4] As a viral oncoprotein, it manipulates host pathways without known small-molecule drugs, positioning it as a key target for HPV-related therapeutic interventions like vaccines or peptide inhibitors.[1][9]

Other names

HPV16 E6 proteinE6 oncoproteinE6 transforming protein