Human herpesvirus-6B protein U19 contains a p53 BOX I homology motif for HDM2 binding and p53 stabilization.
Virology
; 448: 33-42, 2014 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-24314634
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Transactivadores
/
Proteína p53 Supresora de Tumor
/
Herpesvirus Humano 6
/
Infecciones por Roseolovirus
/
Proteínas Proto-Oncogénicas c-mdm2
Límite:
Humans
Idioma:
En
Revista:
Virology
Año:
2014
Tipo del documento:
Article
País de afiliación:
Dinamarca