E6 oncoprotein from human papillomavirus type 16 (HPV-16 E6) (HPV-16 E6 or E6)

HPV-16 E6 is a small viral oncoprotein (approximately 150 amino acids) produced by human papillomavirus type 16, a high-risk mucosal HPV strongly associated with cervical and anogenital cancers. The protein functions as a multivalent adapter that promotes cellular transformation through multiple mechanisms, most prominently by mediating the degradation of the p53 tumor suppressor protein via formation of a heterotrimeric complex with the cellular ubiquitin ligase E6AP. Beyond p53 degradation, HPV-16 E6 uniquely binds directly to the transcription factor IRF3 to suppress the type I interferon antiviral response, a property that distinguishes it from other high-risk HPV types and may explain its elevated prevalence in HPV-associated cancers. The protein contains two zinc-binding domains (N-terminal and C-terminal) connected by a linker region; the N-terminal domain mediates homodimerization, which is essential for E6's transforming functions, while the C-terminal domain recruits target proteins. HPV-16 E6 also interacts with the transcriptional coactivator CBP/p300 and targets multiple PDZ domain-containing tumor suppressors for degradation. As a viral oncoprotein critical to HPV-driven malignant transformation, HPV-16 E6 represents a major therapeutic target for cancer prevention and treatment, primarily through vaccine-based and immunotherapeutic approaches rather than direct inhibition of the protein itself.

Other names

E6 proteinTransforming protein E6E6*HPV16 E6High-risk HPV E6 protein

Direct binding to p53 via E6AP (E6-associated protein/UBE3A) complex formation, leading to p53 ubiquitination and proteasomal degradation; Binding to IRF3 transcription factor to inhibit type I interferon response; Interaction with CBP/p300 coactivators to suppress p53 transcriptional activity; Recruitment and degradation of PDZ domain-containing tumor suppressors (such as hDlg and MAGI-1); Homodimerization through N-terminal domain, which is necessary for p53 degradation activity