Identification of a novel retrovirus long terminal repeat (LTR) that is targeted by p51A (TAp63gamma) and selective dominant-negative activity of p73L (DeltaNp63alpha) toward p53-responsive promoter activities.
The p51/p73L/p63/p40 gene, recently identified as a p53 homolog, encodes two major isoforms, p51A and p73L, which are suggested to have similar functions synonymous with p53 and dominant-negative activity toward both p53 and p51A, respectively. We have cloned a high affinity genomic fragment bound to p51A that was assigned to be a novel retrovirus long terminal repeat. Strikingly, this fragment was found to bind to both p53 and p73L with similar affinity to p51A. Additional demonstration with known p53 response elements suggested that DNA-binding profiles of p51A and p73L were very similar but were distinct from that of p53. Consistent with this novel finding, transient cotransfection experiments in mammalian cells suggested that p73L, when it was expressed at a low level, selectively suppressed p53-dependent transactivation of p21-luc and mdm2-luc but not of cyclinG-luc and bax-luc reporters. These data raise the possibility that p73L differentially modulates the p53 function according to the distinct DNA-binding affinity between these two proteins.
Senoo
M
M
Department of Immunology, Tokai University School of Medicine, Bouseidai, Isehara, Kanagawa, 259-1193, Japan.
Matsumura
Y
Y
Habu
S
S
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins; D011401:Promoter Regions, Genetic; D012190:Retroviridae / Q000235:genetics*; D020079:Terminal Repeat Sequences; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins