TIGHT DNA-BINDING AND OLIGOMERIZATION ARE DISPENSABLE FOR THE ABILITYOF P53 TO TRANSACTIVATE TARGET GENES AND SUPPRESS TRANSFORMATION

The p53 tumor suppressor protein can bind tightly to specific sequence elements in the DNA and induce the transactivation of genes harboring such p53 binding sites. Various lines of evidence suggest that p53 bi nds to its target site as an oligomer. To test whether oligomerization is essential for the biological and biochemical activities of p53, we deleted a major part of the dimerization domain of mouse wild-type p5 3. The resultant protein, termed p53wtDELTASS, was shown to be incapab le of forming detectable homo-oligomers in vitro and is, therefore, li kely to be predominantly if not exclusively monomeric. In agreement wi th the accepted model, p53wtDELTASS indeed failed to exhibit measurabl e DNA binding in vitro. Surprisingly, though, it was still capable of suppressing oncogene-mediated transformation and of transactivating in vivo a target gene containing p53 binding sites. These findings indic ate that dimerization-defective p53 is biologically active and may eng age in productive sequence-specific DNA interactions in vivo. Furtherm ore, p53 dimerization probably leads to cooperative binding to specifi c DNA sequences.