Hepcidin, a key regulator of iron metabolism, is transcriptionally activated by p53

Br J Haematol. 2007 Jul;138(2):253-62. doi: 10.1111/j.1365-2141.2007.06638.x.


Hepcidin is an iron-regulatory protein that is upregulated in response to increased iron or inflammatory stimuli. Hepcidin reduces serum iron and induces iron sequestration in the reticuloendothelial macrophages - the hallmark of anaemia of inflammation. Iron deprivation is used as a defense mechanism against infection, and it also has a beneficial effect on the control of cancer. The tumour-suppressor p53 transcriptionally regulates genes involved in growth arrest, apoptosis and DNA repair, and perturbation of p53 pathways is a hallmark of the majority of human cancers. This study inspected a role of p53 in the transcriptional regulation of hepcidin. Based on preliminary bioinformatics analysis, we identified a putative p53 response-element (p53RE) contained in the hepcidin gene (HAMP) promoter. Chromatin immunoprecipitation (ChIP), reporter assays and a temperature sensitive p53 cell-line system were used to demonstrate p53 binding and activation of the hepcidin promoter. p53 bound to hepcidin p53RE in vivo, andthis p53RE could confer p53-dependent transcriptional activation. Activation of p53 increased hepcidin expression, while silencing of p53 resulted in decreased hepcidin expression in human hepatoma cells. Taken together, these results define HAMP as a novel transcriptional target of p53. We hypothesise that hepcidin upregulation by p53 is part of a defence mechanism against cancer, through iron deprivation. Hepcidin induction by p53 might be involved in the pathogenesis of anaemia accompanying cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides / genetics*
  • Antimicrobial Cationic Peptides / metabolism
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Hepcidins
  • Humans
  • Interleukin-6 / genetics
  • Iron / metabolism*
  • Mutation
  • RNA Interference / physiology
  • RNA, Small Interfering / genetics
  • Response Elements / genetics
  • Transcription, Genetic / genetics
  • Tumor Suppressor Protein p53 / genetics*


  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • Hepcidins
  • Interleukin-6
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Iron