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The molecular mechanism and potential role of heat shock-induced p53 protein accumulation

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Abstract

Workers who are exposed to extreme heat or work in hot environments may be at risk of heat stress. Exposure to extreme heat can result in occupational illnesses and injuries. On the other hand, local and regional heat therapy has been used for the treatment of some cancers, such as liver cancer, lung cancer, and kidney cancer. Although heat stress has been shown to induce the accumulation of p53 protein, a key regulator of cell cycle, apoptosis, DNA repair, and autophagy, how it regulates p53 protein accumulation and what the p53 targets are remain unclear. Here, we show that, among various genotoxic stresses, including ionizing radiation (IR) and ultraviolet (UV) radiation, heat stress contributes significantly to increase p53 protein levels in normal liver cells and liver cancer cells. Heat stress did not increase p53 mRNA expression as well as p53 promoter activity. However, heat stress enhanced the half-life of p53 protein. Moreover, heat stress increased the expression of puma and light chain 3 (LC-3), which are associated with the apoptotic and autophagic function of p53, respectively, whereas it did not change the expression of the cell cycle regulators p21, 14-3-3δ, and GADD45α, suggesting that heat-triggered alteration of p53 selectively modulates the downstream targets of p53. Our study provides a novel mechanism by which heat shock stimulates p53 protein accumulation, which is different from common DNA damages, such as IR and UV, and also provides new molecular basis for heat injuries or heat therapy.

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Acknowledgments

This work was supported by National Natural Science Foundation (31100604, 81101065, 30972594, and 81272913).

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Authors and Affiliations

  1. Institute of Hepatology, Beijing Military General Hospital, Beijing, 100700, People’s Republic of China

    Juqiang Han

  2. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd., Beijing, 100850, People’s Republic of China

    Juqiang Han, Xiaojie Xu, Zhongyi Fan, Lei Kang, Jing Fu, Jiahong Liu & Qinong Ye

  3. Department of General Surgery, 305 Hospital of PLA, Beijing, People’s Republic of China

    Hongzhen Qin

  4. Department of Cardiology, 307 Hospital of PLA, Beijing, 100071, People’s Republic of China

    Anheng Liu

  5. Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, People’s Republic of China

    Lei Kang

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  1. Juqiang Han
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Correspondence to Qinong Ye.

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Juqiang Han, Xiaojie Xu, Hongzhen Qin, and Anheng Liu contributed equally to this study.

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Han, J., Xu, X., Qin, H. et al. The molecular mechanism and potential role of heat shock-induced p53 protein accumulation. Mol Cell Biochem 378, 161–169 (2013). https://doi.org/10.1007/s11010-013-1607-9

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  • DOI: https://doi.org/10.1007/s11010-013-1607-9

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