SCIENCE@home

Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function

Jia Shen,Xiangpeng Sheng,ZeNan L. Chang,Qian Wu,Sheng Wang,Zongliang Xuan,Dan Li,Yalan Wu,Yongjia Shang,Xiangtao Kong,Long Yu,Lin Li,Kangcheng Ruan,Hongyu Hu,Ying Huang,Lijian Hui,Dongling Xie,Fudi Wang,Ronggui Hu

Published 2014 in Cell Reports

ABSTRACT

SUMMARY 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-67 of 67 references · Page 1 of 1

CITED BY

Showing 1-100 of 216 citing papers · Page 1 of 3

123
Next