The identification of a conserved binding motif within human papillomavirus type 16 E6 binding peptides, E6AP and E6BP.

Induction of apoptosis in human papillomaviruspositive cancer cells by peptide aptamers targeting the viral E6 oncoprotein

“…Interestingly, 6 of 17 peptide aptamers contained Cys-residues spaced as C-X-X-C (E61-1, -5, -9, -12, -14, and -16), raising the possibility that they interact with E6, which itself contains four C-X-X-C sequences, via chelating zinc. Furthermore, although not exactly matching the consensus sequences proposed for the interaction domains of some cellular E6 binding factors (37,38), several of the peptides isolated in this study were characterized by the presence of hydrophobic residues in similar motifs (e.g., D-I-L-G-related sequences, such as D-V-L-G in E61-2). In addition, however, HPV16 E6 was also bound by peptides that did not have obvious sequence homologies to known natural binding partners, such as the potent growth inhibitor E61-1.…”

The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-α

“…A recent study with the`high risk' HPV-16 E6 led to the identi®cation of the conserved binding motif E-L-L/V-G within the E6 interacting proteins E6AP (a ubiquitin protein ligase) and E6BP (a putative calcium binding protein), which is required for interaction with HPV-16 E6 (Elston et al, 1998). Analysis of the amino acid sequences of Tyk2 identi®ed the presence of a similar sequence E-S-L-G within the JH6 domain of Tyk2 supporting our data that this domain is required for E6/Tyk2 interaction (Figure 8).…”

The Human Papillomavirus E6 protein and its contribution to malignant progression

“…Another conserved binding site, the L2G box which comprises a a-helical motif, has been found on a number of cellular targets of E6, including E6AP, hMcm7, E6BP and paxillin. The binding speci®city of E6AP is mediated by this motif, present on both enzyme and substrate, and this in turn is used by E6 to interact with both (Chen et al, 1998;Elston et al, 1998;KuÈ hne and Banks, 1998). Not surprisingly, E6 has also been reported to induce self-ubiquitination of E6AP (Kao et al, 2000), nonetheless, there are proteins which interact with E6 through an L2G box without being targeted for degradation, such as E6BP (Chen et al, 1995) and paxillin (Tong and Howley, 1997).…”