Topors, a p53 and topoisomerase I binding protein, interacts with the adeno-associated virus (AAV-2) Rep78/68 proteins and enhances AAV-2 gene expression.
The adeno-associated virus type 2 (AAV-2) Rep proteins are essential for AAV DNA replication and regulation of AAV gene expression. We have identified a cellular protein interacting with Rep78 and Rep68 in yeast two-hybrid analysis and in GST pull-down assays. This protein has recently been described as both a p53 (p53BP3) and a topoisomerase I interacting protein (Topors). It contains an arginine/serine-rich domain, a RING finger domain and five PEST sequences. A minimal sequence sufficient for interaction with Rep was mapped to Topors amino acids 871 to 917. We show that the same region is also involved in the interaction with p53. Rep sequences involved in interaction with Topors were mapped to Rep amino acids 172 to 481. Overexpression of Topors stimulated AAV gene expression in the absence of helper virus, suggesting a function of Topors as a transcriptional regulator.
Weger
Stefan
S
Institut für Infektionsmedizin, Abteilung Virologie, Freie Universität Berlin, Hindenburgdamm 27, D-12203 Berlin, Germany1.
Hammer
Eva
E
Institut für Infektionsmedizin, Abteilung Virologie, Freie Universität Berlin, Hindenburgdamm 27, D-12203 Berlin, Germany1.
Heilbronn
Regine
R
Institut für Infektionsmedizin, Abteilung Virologie, Freie Universität Berlin, Hindenburgdamm 27, D-12203 Berlin, Germany1.
D020816:Amino Acid Motifs; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006378:Helper Viruses / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; C068734:rep proteins, Adeno-associated virus 2; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases; D004264:DNA Topoisomerases, Type I