Human herpesvirus-6B protein U19 contains a p53 BOX I homology motif for HDM2 binding and p53 stabilization

Emil Kofod-Olsen, Susanne Pettersson, Maura Wallace, Ahmed Basim Abduljabar, Bodil Oster, Ted Hupp, Per Hollsberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In order to establish a successful infection, it is of crucial importance for invading viruses to alter the activities of the regulatory protein p53. Beta-herpesviruses stabilize p53 and likely direct its activities towards generation of a replication-friendly environment. We here study the mechanisms behind HHV-6B-induced stabilization and inactivation of p53. Stable transgene expression of the HHV-6B protein U19 was sufficient to achieve upregulation of p53. U19 bound directly to the p53-regulating protein HDM2 in vitro, co-precipitated together with HDM2 in lysates, and co-localized with HDM2 in the nucleus when overexpressed. U19 contained a sequence with a putative p53 BOX I-motif for HDM2 binding. Mutation of the two key amino acids within this motif was sufficient to inhibit all the described U19 functions. Our study provides further insight into p53-modulating strategies used by herpesviruses and elucidates a mechanism used by HHV-6B to circumvent the antiviral response. (C) 2013 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)33-42
Number of pages10
JournalVirology
Volume448
DOIs
Publication statusPublished - 5 Jan 2014

Keywords

  • Human herpesvirus-6B
  • p53
  • U19
  • Virus-cell interactions
  • HDM2
  • HUMAN CYTOMEGALOVIRUS
  • DNA-DAMAGE
  • HODGKINS LYMPHOMA
  • T-CELLS
  • MDM2
  • INFECTION
  • EXPRESSION
  • 6B
  • PHOSPHORYLATION
  • UBIQUITINATION

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