AUGMENTED DNA-BINDING ACTIVITY OF P53 PROTEIN ENCODED BY A CARBOXYL-TERMINAL ALTERNATIVELY SPLICED MESSENGER-RNA IS BLOCKED BY P53 PROTEIN ENCODED BY THE REGULARLY SPLICED FORM

DNA-binding activity of the wild-type p53 is central to its function i n vivo. However, recombinant or in vitro translated wild-type p53 prot eins, unless modified, are poor DNA binders, The fact that the in vitr o produced protein gains DNA-binding activity upon modification at the C terminus raises the possibility that similar mechanisms may exist i n the cell. Data presented here show that a C-terminal alternatively s pliced wild-type p53 (ASp53) mRNA expressed by bacteria or transcribed in vitro codes for a p53 protein that efficiently binds DNA. Our resu lts support the conclusion that the augmented DNA binding activity of an ASp53 protein is probably due to attenuation of the negative effect residing at the C terminus of the wild-type p53 protein encoded by th e regularly spliced mRNA (RSp53) rather than acquisition of additional functionality by the alternatively spliced C' terminus. In addition, we found that ASp53 forms a complex with the non-DNA-binding RSp53, wh ich in turn blocks the DNA-binding activity of ASp53. Interaction betw een these two wild-type p53 proteins may underline a mechanism that co ntrols the activity of the wild-type p53 protein in the cell.