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The p53 protein is a sequence-specific transcription factor controllingthe expression of multiple genes and protecting cells from oncogenic transformation.In many tumors, the p53 protein is completely or partially inactivated by mutationsin the p53 gene. We analyzed the transactivating activity of nine human temperature-dependent(td) p53 mutants in yeast cells. Mutations in seven of them were localized inthe β-sandwich-coding region of the p53 gene, eight p53 mutants were temperature-sensitiveand the R283C mutant was cold-sensitive. Patterns of their transactivation abilitiestowards three different responsive elements, the extent of their temperature dependencyas well as discriminativity, were considerably variable. Similarly, their capacityto become reactivated by amifostine varied from complete resistance to high sensitivity.Transactivation abilities and temperature dependency of six p53 td mutants weredetermined in transiently-transfected H1299 human cells and revealed substantialconcordance between the activity patterns of the p53 mutants in yeast and humancells. We concluded that the td p53 mutants do not comprise a uniform group, therefore,the behavior of each mutant has to be tested individually.

Transactivation and reactivation capabilities of temperature-dependent p53 mutants in yeast and human cells