SMALL PEPTIDES ACTIVATE THE LATENT SEQUENCE-SPECIFIC DNA-BINDING FUNCTION OF P53

Normal cells contain p53 protein in a latent state that can be activat ed for sequence-specific transcription by low levels of UV radiation w ithout an increase in protein levels. Microinjection of cells with an antibody specific to the C-terminal negative regulatory domain can act ivate the function of p53 as a specific transcription factor in the ab sence of irradiation damage, suggesting that posttranslational modific ation of a negative regulatory domain in vivo is a rate-limiting step for p53 activation. Small peptides derived from the negative regulator y domain of p53 have been used as biochemical tools to distinguish bet ween allosteric and steric mechanisms of negative regulation of p53 te tramer activity. Presented is the development of a highly specific pep tide activation system that is consistent with an allosteric mechanism of negative regulation and that forms a precedent for the synthesis o f novel low molecular mass modifiers of the p53 response.