Regulation of p53 Protein Function in Response to Heat Shock
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p53 protein encoded by the TP53 gene performs one of the most important functions in the process of human tumor suppression. Mutations in the DNA-binding domain of p53 change its conformation, which contributes to the formation of aberrant intracellular protein complexes including heat shock proteins (Hsp70). This can provoke an occurrence of the aggressive types of tumors including breast cancer. Thereby, the study of the regulation mechanisms of mutant p53 in these stable complexes seems extremely relevant. The aim of this work was to study the regulation of p53 protein mutant for R175H (mutp53−R175H) under heat stress in MDA–MB-231 breast cancer cells in vitro. It was found that heat shock caused a drastic decrease in the level of wtp53 (wild-type p53) and mutp53–R175H proteins. It was gradually restored after the stress ceased. We also have found that mutp53–R175H increases the intracellular level of Hsp70 in normal conditions and reduces it after heat shock. At the same time, mutp53–R175H protein changes its intracellular localization, both in normal conditions and in response to heat shock being in the composition of Hsp70 protein complexes. Thus, the behavior of wtp53 and mutp53–R175H in response to heat shock appears to differ due to different interactions with protein complexes that regulate their stability and intracellular localization.
Keywords:p53 R175H mutant p53 heat shock protein Hsp70 Hsp90 Mdm2
This study was supported by the Russian Science Foundation, project no. 14-50-00068.
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interests. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.
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