P53 BINDS TO THE TATA-BINDING PROTEIN-TATA COMPLEX

Earlier reports show that p53, both wild type and mutants, may affect transcription. Wild-type p53 activates promoters with p53-binding site s while inhibiting promoters without binding sites. Mutant p53, on the other hand, has been shown to activate transcription from specific pr omoters. These observations suggest that both wild-type and mutant p53 may interact with a general transcription factor(s). In this report, we have shown that the cloned TATA-binding protein (TBP) from human an d yeast interacts with human p53. TBP coimmunoprecipitates with wild-t ype or mutant human p53 when incubated with the p53-specific monoclona l antibody and Protein A-agarose. Wild-type murine p53 has also been f ound to interact with human TBP. Protein blot assays have demonstrated that the interaction between p53 and human TBP is direct. By gel rete ntion analysis, we have shown that the complex of TBP and p53 (both wi ld type and mutant) can bind to the TATA box. The similar qualitative binding capability of wild-type and mutant p53 with human TBP and the similarity of the two complexes in binding to the TATA box suggest tha t the functional discrimination between wild-type and mutant p53 may n ot lie in their ability to bind TBP. The nature of the p53.TBP or p53. TBP.TATA complex may determine the success of transcription.