title: Transcriptional regulation of HIV-1 gene expression by p53.
abstract: Several reports have pointed to the negative involvement of p53 in transcriptional regulation of the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR). However, the mechanisms of this negative effect remain unclear. In here, we showed that over expression of p53 wild type prevented the phosphorylation of serine 2 in the carboxyl terminal domain (CTD) of RNA polymerase II. As a result of this inhibition, p53 stalled transcriptional elongation on the HIV-1 LTR leading to a significant reduction of HIV-1 replication in primary microglia and astrocytes. However, despite the delay/pause caused by p53, viral transcription and replication decreased and then salvaged. These studies suggest that the negative effect of p53 is alleviated by a third factor. In this regard, our Preliminary Data point to the involvement of the Pirh2 protein in p53 inhibition. Therefore, we suggest that p53 may be a novel therapeutic target for the inhibition of HIV-1 gene expression and replication and the treatment of AIDS.
authors.affiliation: Molecular Virology Lab, Department of Neurology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Ruma
authors.initials: R
authors.lastname: Mukerjee
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
authors.forename: J Robert
authors.initials: JR
authors.lastname: Chang
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Bassel E
authors.initials: BE
authors.lastname: Sawaya
mesh_terms: D002478:Cells, Cultured; D042863:Cyclin-Dependent Kinase 9 / Q000032:analysis / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014779:Virus Replication
chemical_list: D016159:Tumor Suppressor Protein p53; D012694:Serine; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II