The present invention provides isolated polypeptides of human p53 that contain mutations. These mutations can be toxic mutations, supertransactivating mutations or tox-suppressor mutations. Further provided by the invention are methods of identifying toxic, supertransactivating, weak transactivating and tox-suppressor mutations as well as methods of identifying compounds that mimic the toxic, supertransactivating and tox-suppressor mutations in human p53. Also provided are methods of inducing toxicity in a cell by administering a polypeptide comprising a supertransactivating or a toxic mutation.