Transactivation and reactivation capabilities of temperature-dependent             p53 mutants in yeast and human cells.
The p53 protein is a sequence-specific transcription factor controlling             the expression of multiple genes and protecting cells from oncogenic transformation.             In many tumors, the p53 protein is completely or partially inactivated by mutations             in 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 in             the β-sandwich-coding region of the p53 gene, eight p53 mutants were temperature-sensitive             and the R283C mutant was cold-sensitive. Patterns of their transactivation abilities             towards three different responsive elements, the extent of their temperature dependency             as well as discriminativity, were considerably variable. Similarly, their capacity             to become reactivated by amifostine varied from complete resistance to high sensitivity.             Transactivation abilities and temperature dependency of six p53 td mutants were             determined in transiently-transfected H1299 human cells and revealed substantial             concordance between the activity patterns of the p53 mutants in yeast and human             cells. We concluded that the td p53 mutants do not comprise a uniform group, therefore,             the behavior of each mutant has to be tested individually.
Department of Pathology, University Hospital Brno, 625 00 Brno,                     Czech Republic.
Jana
J
Jagosova
Lenka
L
Pitrova
Jana
J
Slovackova
Barbora
B
Ravcukova
Jan
J
Smarda
Jana
J
Smardova
D004999:Amifostine / Q000494:pharmacology; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013696:Temperature; D015533:Transcriptional Activation; D014170:Transformation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics*
D011837:Radiation-Protective Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004999:Amifostine