HPV16 E6 protein (E6)

The HPV16 E6 protein is a small viral oncoprotein (~150 amino acids) expressed by high-risk human papillomavirus type 16, consisting of two homologous zinc-binding domains (E6N and E6C) connected by a flexible linker. It plays a central role in viral oncogenesis by recruiting the E3 ubiquitin ligase E6AP via a conserved LxxLL motif, forming a ternary complex that targets the tumor suppressor p53 for ubiquitination and proteasomal degradation, thereby promoting cell immortalization and blocking apoptosis. E6 also undergoes homodimerization through its N-terminal domain, which is essential for efficient p53 degradation, and interacts with IRF3 to inhibit the type I interferon response, aiding viral persistence. Additional functions include altering transcription, interfering with cell polarity, and degrading other host proteins. In HPV16-infected cells, E6 expression correlates with p53 loss and is a hallmark of cervical cancer and other HPV-associated malignancies. Structural studies reveal a treble clef-like fold in its domains, with distinct surface properties enabling protein interactions, and mutations disrupting these interfaces impair oncogenic activity. While no approved small-molecule drugs directly target E6, its role makes it a focus for therapeutic vaccines and inhibitors in HPV-driven cancers.

Other names

HPV16 E6 oncoproteinE6 oncoproteintransforming protein E6*