Publication details

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

Authors

JAGOŠOVÁ Jana PITROVÁ Lenka SLOVÁČKOVÁ Jana RAVČUKOVÁ Barbora ŠMARDA Jan ŠMARDOVÁ Jana

Year of publication 2012
Type Article in Periodical
Magazine / Source International Journal of Oncology
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.3892/ijo.2012.1520
Field Oncology and hematology
Keywords p53; transactivation; temperature-dependent p53 mutants; discriminating p53 mutants; functional analysis of separated alleles in yeast
Description 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 beta-sandwich-coding region of the p53 gene, eight p53 mutants were temperature-sensitive and the R283C mutant was coldsensitive. 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.
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