例如:"lncRNA", "apoptosis", "WRKY"

p53 Protects Cells from Death at the Heatstroke Threshold Temperature.

Cell Rep. 2019 Dec 10;29(11):3693-3707.e5
Lu Gong 1 , Qinghe Zhang 2 , Xiao Pan 2 , Shuming Chen 2 , Lina Yang 2 , Bin Liu 3 , Weijun Yang 2 , Luyang Yu 2 , Zhi-Xiong Xiao 4 , Xin-Hua Feng 5 , Haihe Wang 3 , Zhi-Min Yuan 6 , Jinrong Peng 7 , Wei-Qiang Tan 8 , Jun Chen 9
Lu Gong 1 , Qinghe Zhang 2 , Xiao Pan 2 , Shuming Chen 2 , Lina Yang 2 , Bin Liu 3 , Weijun Yang 2 , Luyang Yu 2 , Zhi-Xiong Xiao 4 , Xin-Hua Feng 5 , Haihe Wang 3 , Zhi-Min Yuan 6 , Jinrong Peng 7 , Wei-Qiang Tan 8 , Jun Chen 9
+ et al

[No authors listed]

Author information
  • 1 MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
  • 2 MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
  • 3 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, 74 Second Zhonshan Road, Guangzhou 510080, China.
  • 4 Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610064, China.
  • 5 Life Sciences Institute and Innovation Center for Signaling Network, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou 310058, China.
  • 6 Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
  • 7 College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou 310058, China.
  • 8 Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun Road East, Hangzhou 310016, China. Electronic address: tanweixxxx@zju.edu.cn.
  • 9 MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: chenjun2009@zju.edu.cn.

摘要


When the core body temperature is higher than 40°C, life is threatened due to heatstroke. Tumor repressor p53 is required for heat-induced apoptosis at hyperthermia conditions (>41°C). However, its role in sub-heatstroke conditions (≤40°C) remains unclear. Here, we reveal that both zebrafish and human p53 promote survival at 40°C, the heatstroke threshold temperature, by preventing a hyperreactive heat shock response (HSR). At 40°C, both Hsf1 and Hsp90 are activated. Hsf1 upregulates the expression of Hsc70 to trigger Hsc70-mediated protein degradation, whereas Hsp90 stabilizes p53 to repress the expression of Hsf1 and Hsc70, which prevents excessive HSR to maintain cell homeostasis. Under hyperthermia conditions, ATM is activated to phosphorylate p53 at S37, which increases BAX expression to induce apoptosis. Furthermore, growth of p53-deficient tumor xenografts, but not that of their p53+/+ counterparts, was inhibited by 40°C treatment. Our findings may provide a strategy for individualized therapy for p53-deficient cancers.

KEYWORDS: ATM, Hsc70, Hsf1, Hsp90, cell death, heatstroke threshold temperature, human cell, hyperthermia temperature, p53, zebrafish