Loss of the E6AP Ubiquitin Ligase Induces p53-Dependent Phosphorylation of Human Papillomavirus 18 E6 in Cells Derived from Cervical Cancer
Arushi Vats, Neva Skrabar, Giannino Del Sal, Lawrence Banks
Abstract
This study demonstrates that the knockdown of E6AP from cervical cancer-derived cells leads to an increase in phosphorylation of the E6 oncoprotein. We show that this phosphorylation of E6 requires p53 transcriptional activity and the enzyme DNA PK. This study therefore defines a feedback loop whereby activation of p53 can induce phosphorylation of E6 and which in turn can inhibit p53 transcriptional activity independently of E6's ability to target p53 for degradation.
Topics & Concepts
PhosphorylationSerineBiologyKinaseGene knockdownPhosphoserinePhosphorylation cascadeUbiquitin ligaseCell biologyDownregulation and upregulationThreonineSUMO proteinMolecular biologyTranscription (linguistics)Protein phosphorylationUbiquitinSignal transductionCancer researchProtein kinase ATranscription factorDNA damageDNADNA ligaseProtein-Serine-Threonine KinasesMdm2PDZ domainEnzyme activatorDNA-binding proteinTranscriptional regulationPost-translational regulationRegulation of gene expressionDephosphorylationCancer-related Molecular PathwaysCervical Cancer and HPV ResearchUbiquitin and proteasome pathways