UREB1, a tyrosine phosphorylated nuclear protein, inhibits p53 transactivation.
Tumor suppressor p53 is a transcription activator that upregulates target genes containing the p53 binding site. UREB1, a DNA binding protein that is tyrosine phosphorylated in vivo, shares a significant homology with the human papilloma virus E6 associated protein (E6-AP). E6-AP forms a ternary complex with E6 and p53 and participates in the ubiquitination of p53. Based on the homology with E6-AP, but taking into account the nuclear localization of UREB1 and its smaller size, the present study used a transient transfection system to examine whether UREB1 influenced p53-stimulated transcription. Co-transfection of a vector expressing wildtype UREB1 with one expressing p53 into H1299, a p53 negative cell line, resulted in a pronounced suppression of p53 transactivation. The inhibitory effect was significantly attenuated by mutation of a tyrosine residue in the consensus tyrosine phosphorylation sequence of UREB1. These data suggest that optimal suppression of p53 transactivation requires tyrosine phosphorylated UREB1 and that tyrosine phosphorylation and dephosphorylation processes may be involved in the regulation of p53 transactivation.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016158:Genes, p53; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; C502830:HUWE1 protein, human; D044767:Ubiquitin-Protein Ligases