Identification of a novel retrovirus long terminal repeat (LTR) that is targeted by p51A (TAp63 gamma) and selective dominant-negative activity of p73L (Delta Np63 alpha) toward p53-responsive promoter activities

The p51/p73L/p63/p40 gene, recently identified as a p53 homolog, encodes tw o major isoforms, p51A and p73L, which are suggested to have similar functi ons synonymous with p53 and dominant-negative activity toward both p53 and p51A, respectively. We have cloned a high affinity genomic fragment bound t o p51A that was assigned to be a novel retrovirus long terminal repeat. Str ikingly, 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, transie nt cotransfection experiments in mammalian cells suggested that p73L, when it was expressed at a low level, selectively suppressed p53-dependent trans activation of p21-luc and mdm2-luc but not of cyclinG-luc and bax-luc repor ters. These data raise the possibility that p73L differentially modulates t he p53 function according to the distinct DNA-binding affinity between thes e two proteins. (C) 2001 Academic Press.