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Virology ; 460-461: 45-54, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25010269

ABSTRACT

Analysis of the herpes simplex virus-1 (HSV-1) genome reveals two candidate p53 responsive elements (p53RE), located in proximity to the replication origins oriL and oriS, referred to as p53RE-L and p53RE-S, respectively. The sequences of p53RE-L and p53RE-S conform to the p53 consensus site and are present in HSV-1 strains KOS, 17, and F. p53 binds to both elements in vitro and in virus-infected cells. Both p53RE-L and p53RE-S are capable of conferring p53-dependent transcriptional activation onto a heterologous reporter gene. Importantly, expression of the essential immediate early viral transactivator ICP4 and the essential DNA replication protein ICP8, that are adjacent to p53RE-S and p53RE-L, are repressed in a p53-dependent manner. Taken together, this study identifies two novel functional p53RE in the HSV-1 genome and suggests a complex mechanism of viral gene regulation by p53 which may determine progression of the lytic viral replication cycle or the establishment of latency.


Subject(s)
Gene Expression Regulation, Viral , Genome, Viral , Herpes Simplex/metabolism , Herpesvirus 1, Human/genetics , Response Elements , Tumor Suppressor Protein p53/metabolism , Base Sequence , Down-Regulation , Herpes Simplex/genetics , Herpes Simplex/virology , Herpesvirus 1, Human/metabolism , Humans , Molecular Sequence Data , Protein Binding , Replication Origin , Tumor Suppressor Protein p53/genetics
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