Dec 24, 1999 · HPV E6 induces the degradation of p53. The E1 ubiquitin-activating enzyme activates ubiquitin (Ub), which is transferred by the E2 ubiquitin-conjugating enzyme to the E3...

Dec 13, 1999 · The E6 protein of the oncogenic, mucosal-specific HPV types has been shown to complex with p53 and, as a result, target it for rapid proteasome-mediated degradation. As a consequence, p53's growth-arrest and apoptosis-inducing activities are abrogated.

Jan 28, 2016 · Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6.

Mar 6, 2025 · Kenny et al. characterized the complex structure of full-length E6AP with E6 and p53, a prerequisite for p53 ubiquitination by E6AP. This structure highlights an N-terminal ordered domain (NOD) of E6AP.

In this study, we show that a p53 dominant negative mutant or USP15 increase E6 stability by blocking the ubiquitination of E6, impair E6-induced p53 degradation and enhance p53-dependent tumor suppression.

Recent experiments demonstrated that three E6 single-site mutants (F47R, R102A, and L50E) can inhibit the E6/E6AP/p53 heterotrimer formation and rescue p53 from the degradation pathway. However, the molecular mechanism underlying mutation-induced heterotrimer inhibition remains largely elusive.

Feb 7, 2025 · A main transforming activity of the anti-apoptotic E6 oncoprotein [7] is the formation of a trimeric complex with the cellular ubiquitin ligase E6AP (E6-associated protein, encoded by the UBE3A gene) and the tumor suppressor protein p53, leading to …

The authors found that both tagged versions of HPV-11E6 are primarily expressed in the cytoplasm and further that overexpression of HPV-11E6 results in cytoplasmic translocation of p53, binding of p53 to BAK, and induction of apoptosis (See Figure 1).

Oct 11, 2019 · The human papillomavirus (HPV) oncoprotein E6 specifically binds to E6AP (E6-associated protein), a HECT (homologous to the E6AP C terminus)-type ubiquitin ligase, and directs its ligase activity toward the tumor suppressor p53.

The human papillomavirus (HPV) oncoprotein E6 specifically binds to E6AP (E6-associated protein), a HECT (homologous to the E6AP C terminus)-type ubiquitin ligase, and directs its ligase activity toward the tumor suppressor p53.