Isolation of p53 Inhibitors by Screening Chemical Libraries in Cell-Based Readout System

p53 is a key mediator of cell response to a variety of stresses, inducing growth arrest or apoptosis, thereby eliminating damaged and potentially dangerous cells from the organism (1 ,2 ). Once p53-dependent mechanisms are broken, conditions for rapid accumulation of genetic changes are established, leading to dramatic destabilization of the genome and acceleration of carcinogenesis. Indeed, in the majority of tumors, p53-mediated response is broken either by inactivation of the p53 gene itself (3 ,4 ), by other members of the pathway (Arf) (5 ), or by natural negative p53 regulators of cellular (Mdm2) (6 ) or viral (E6) (7 ,8 ) origin.