Analysis of transactivation capability and conformation of p53 temperature-dependent mutants and their reactivation by amifostine in yeast.
The p53 gene is often mutated during cancer development. Frequency and functional consequences of these mutations vary in different tumor types. We analysed conformation and temperature dependency of 23 partially inactivating temperature-dependent (td) p53 mutants derived from various human tumors in yeast. We found considerable differences in transactivation capabilities and discriminative character of various p53 mutants. No correlations in transactivation rates and conformations of the td p53 proteins were detected. Amifostine-induced p53 reactivation occurred only in 13 of 23 td mutants, and this effect was temperature dependent and responsive element specific. The most of the p53 mutations (10/13) reactivated by amifostine were located in the part of the p53 gene coding for hydrophobic beta-sandwich structure of the DNA-binding domain.
Grochova
D
D
Department of Pathology, University Hospital, Brno, Czech Republic.
Vankova
J
J
Damborsky
J
J
Ravcukova
B
B
Smarda
J
J
Vojtesek
B
B
Smardova
J
J
D004999:Amifostine / Q000494:pharmacology*; D019943:Amino Acid Substitution / Q000235:genetics*; D006801:Humans; D011487:Protein Conformation / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects / Q000235:genetics*; D013696:Temperature; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*
D011837:Radiation-Protective Agents; D029701:Saccharomyces cerevisiae Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004999:Amifostine