Ferritin binds and activates p53 under oxidative stress.
Ferritin, an iron storage protein, plays an essential role in iron homeostasis and a wide range of physiologic processes. Ferritin alleviates oxidative stress by regulating cellular labile iron concentration. The tumor suppressor p53 is induced upon iron depletion, and controls reactive oxygen species level. Although some functional connections between ferritin and p53 were implied in several reports, the direct links between ferritin and p53 has not yet been investigated. Here we report that ferritin physically interacts with p53 upon oxidative stress. Ferritin increases p53 protein level and p53 transcriptional activity in ferroxidase activity independent manner. Ferritin knocked down cells show retarded induction of p53 target genes upon oxidative stress. These findings suggest that ferritin cooperates with p53 to cope with oxidative stress.
Lee
Jong-Hyuk
JH
National Research Laboratory for Metabolic Checkpoint, Department of Biomedical Sciences & Biochemistry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jang
Hyonchol
H
Cho
Eun-Jung
EJ
Youn
Hong-Duk
HD
D001052:Apoferritins / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D005293:Ferritins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D010088:Oxidoreductases; D055550:Protein Stability; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C507433:FTL protein, human; D016159:Tumor Suppressor Protein p53; D005293:Ferritins; D001052:Apoferritins; C454461:FTH1 protein, human; D010088:Oxidoreductases