Multiple regions of E6AP (UBE3A) contribute to interaction with papillomavirus E6 proteins and the activation of ubiquitin ligase activity.

ABSTRACT: The HECT domain E3 ubiquitin ligase E6AP (UBE3A) is critical for the development of human papillomavirus (HPV) associated cancers, the neurodevelopment disorder Angelman Syndrome, and some cases of autism spectrum disorders. How E6AP recognizes its cellular targets and how its ubiquitin ligase activity is triggered remain poorly understood, and HPV E6 proteins are models for these processes. We examined diverse E6 proteins from human and non-human papillomaviruses and identified two different modes of interaction between E6 and E6AP. In Type I interactions, E6 can interact directly with the LXXLL peptide motif alone of E6AP (isolated from the rest of E6AP), and then recruit cellular substrates such as p53. In Type II interactions, E6 proteins require additional auxiliary regions of E6AP in

SUBMITTER: Drews CM 

PROVIDER: S-EPMC6999913 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature