P53R3

P53R3 is a potent p53 reactivator and restores sequence-specific DNA binding of p53 hot spot mutants, including p53^R175H, p53^R248W?and p53^R273H. P53R3 induces p53-dependent antiproliferative effects with much higher specificity than PRIMA-1. P53R3 enhances the recruitment of wild-type p53 and p53^M237I?to several target gene promoters. P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5). P53R3 is used for cancer research^[1]. In Vitro: P53R3 (10?μg/ml; 24 hours; in the absence or presence of the unlabelled p53 consensus oligonucleotide) restores p53-specific DNA binding activity to p53^R273H (a DNA contact mutant) and p53R175H (a structural mutant) in WiDr colon tumour cells harbouring p53^R273H?and KLE cells with p53R175H^[1].
P53R3 (1-33 μg/ml; 24 hours) inhibits the proliferation of the LN-308 sublines expressing mutant p53 plasmids in a p53-dependent manner. The p53^R175H-dependent effects are strong over a broad range of concentrations, but p53^R273H-dependent effects are weaker and requires high concentrations of P53R3^[1].
P53R3 induces p53^R248W?reactivation is more pronounced proliferation inhibition than observed with p53^R273H. P53R3 does not exhibit cytotoxic effects even at concentrations close to its solubility limit (33?μg/ml)^[1].
P53R3 (33?μg/ml; 18 hours) induces a strong decrease in S phase cells and a G0/G1?cell cycle arrest in LN-308 p53^R175H?and LN-308 p53^R273H cells. But it does not affect cell cycle distribution of LN-308 p53^R248W?cells^[1].