title: The molecular mechanism and potential role of heat shock-induced p53 protein accumulation.
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.
authors: Institute of Hepatology, Beijing Military General Hospital, Beijing, People's Republic of China.
authors: Juqiang
authors: J
authors: Han
authors: Xiaojie
authors: X
authors: Xu
authors: Hongzhen
authors: H
authors: Qin
authors: Anheng
authors: A
authors: Liu
authors: Zhongyi
authors: Z
authors: Fan
authors: Lei
authors: L
authors: Kang
authors: Jing
authors: J
authors: Fu
authors: Jiahong
authors: J
authors: Liu
authors: Qinong
authors: Q
authors: Ye
mesh_terms: D017115:Catheter Ablation; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006207:Half-Life; D018869:Heat-Shock Response; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008156:Luciferases