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

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• 作者：Emil Kofod-Olsen ; Susanne Pettersson ; Maura Wallace ; Ahmed Basim Abduljabar ; Bodil 脴ster ; Ted Hupp ; Per H枚llsberg
• 关键词：Human herpesvirus-6B ; p53 ; U19 ; Virus&ndash ; cell interactions ; HDM2
• 刊名：Virology
• 出版年：5 January, 2014
• 年：2014
• 卷：448
• 期：Complete
• 页码：33-42
• 全文大小：3606 K

文摘

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.