Human papillomavirus type 18 E6 protein (HPV-18 E6) (HPV-18 E6)

The Human papillomavirus type 18 E6 protein is a primary oncoprotein produced by high-risk HPV-18, which is a major causative agent of cervical and other mucosal cancers [UniProt: P06463]. Its primary mechanism of action involves the recruitment of the host cellular E3 ubiquitin ligase, E6AP, to form a complex that specifically targets the tumor suppressor protein p53 for rapid ubiquitin-mediated proteasomal degradation [Scheffner et al., 1990, Cell]. By eliminating p53, E6 effectively bypasses DNA damage checkpoints and inhibits apoptosis, facilitating the accumulation of genetic mutations and promoting malignant transformation [Vande Pol and Klingelhutz, 2013, Virology]. Additionally, E6 interacts with various other cellular proteins, such as PDZ-domain proteins and telomerase (hTERT), to further drive cell proliferation and immortalization [Ho et al., 2021, Cancers]. Therapeutic strategies targeting HPV-18 E6 include DNA vaccines, siRNA-based gene silencing, and small molecule inhibitors designed to disrupt the E6-p53 or E6-E6AP interaction [Inovio Pharmaceuticals, VGX-3100]. Because E6 expression is essential for the maintenance of the malignant phenotype in HPV-positive cancers, it represents a high-value target for precision oncology and immunotherapy [PubMed: 33435233].

Other names

HPV-18 E6 oncoproteinE6 proteinHPV18 E6Early protein 6Protein E6VE6_HPV18

Recruitment of E6AP to target p53 for proteasomal degradation; activation of hTERT; binding to PDZ-domain proteins [Scheffner et al., 1990, Cell; Vande Pol and Klingelhutz, 2013, Virology].