Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function
文献类型：期刊论文
| 作者 | Shen, J; Sheng, XP; Chang, ZN; Wu, Q; Wang, S; Xuan, ZL; Li, D; Wu, YL; Shang, YJ; Kong, XT |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2014 |
| 卷号 | 7期号:1页码:180-193 |
| 通讯作者 | Hu, RG (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,coryhu@sibs.ac.cn |
| 英文摘要 | Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor growth, suggesting that upregulation of wild-type p53 signaling underlies the selective efficacy of iron deprivation. Our findings thus identify a direct link between iron/heme homeostasis and the regulation of p53 signaling, which not only provides mechanistic insights into iron-excess-associated tumorigenesis but may also help predict and improve outcomes in iron-deprivation-based chemotherapy. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | END RULE PATHWAY ; HEREDITARY HEMOCHROMATOSIS ; DNA-DAMAGE ; HEPATOCELLULAR-CARCINOMA ; CANCER ; TACHPYRIDINE ; MUTATIONS ; CHELATORS ; UBIQUITIN ; SENSOR |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000334298200019 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/122]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Shen, J,Sheng, XP,Chang, ZN,et al. Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function[J]. CELL REPORTS,2014,7(1):180-193. |
| APA | Shen, J.,Sheng, XP.,Chang, ZN.,Wu, Q.,Wang, S.,...&Hu, RG.(2014).Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function.CELL REPORTS,7(1),180-193. |
| MLA | Shen, J,et al."Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function".CELL REPORTS 7.1(2014):180-193. |
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