title: Human herpesvirus-6B protein U19 contains a p53 BOX I homology motif for HDM2 binding and p53 stabilization.
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.
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
authors: Emil
authors: E
authors: Kofod-Olsen
authors: Susanne
authors: S
authors: Pettersson
authors: Maura
authors: M
authors: Wallace
authors: Ahmed Basim
authors: AB
authors: Abduljabar
authors: Bodil
authors: B
authors: Oster
authors: Ted
authors: T
authors: Hupp
authors: Per
authors: P
authors: Höllsberg
mesh_terms: D020816:Amino Acid Motifs; D002460:Cell Line; D015654:Herpesvirus 6, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D019349:Roseolovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: HDM2; Human herpesvirus-6B; U19; Virus–cell interactions; p53