Ubiquitin ligase E6AP mediates nonproteolytic polyubiquitylation of β-catenin independent of the E6 oncoprotein

• DOI: 10.1099/jgv.0.000624
• Publication Date: 2016-10-11T16:12:22Z
• Authors: Yael Kuslansky; Sophia Sominsky; Anna Jackman; Cristina Gamell; Brendon J. Monahan; Ygal Haupt; Rina Rosin-Arbesfeld; Levana Sherman
• Keywords: Deubiquitinating enzyme

Recently, we showed that the ubiquitin ligase E6AP stabilizes β-catenin and activates its transcriptional activity. These activities were enhanced by human papillomavirus (HPV) E6 protein. In present study, explored function of E6AP, which increases stabilization activation. Here, report interacts with mediates nonproteolytic ubiquitylation, as evidenced in transiently transfected cell-based vitro reconstitution ubiquitylation assays. Overexpression increased polyubiquitylation and, consistent that, knockdown or knock-out expression reduced polyubiquitylation. The was dependent on E3 activity, but it proteasome-independent did not require HPV-E6, phosphorylation glycogen synthase kinase 3β (GSK3β) activity 'destruction complex'. We also show activation is coupled protein stabilization, ubiquitylation. contrast to stability absolutely destruction complex GSK3β. Collectively, our data uncover a dual role for regulation HPV-E6 enhancing only part activities.