Physical and functional interaction of Runt-related protein 1 with hypoxia-inducible factor-1alpha

Oncogene. 2008 Jan 31;27(6):839-47. doi: 10.1038/sj.onc.1210676. Epub 2007 Aug 6.


Angiogenesis and hematopoiesis are closely linked and interactive with each other, but few studies were given to identify possible links between angiogenesis-promoting proteins and hematopoiesis-related transcription factors. Here we investigated the potential relationship of oxygen-sensitive alpha-subunit of angiogenesis-related hypoxia-inducible factor-1alpha (HIF-1alpha) with Runt-related protein 1 (Runx1, also known as acute myeloid leukemia-1, AML-1), an important hematopoietic transcription factor. The results demonstrated that Runx1 and HIF-1alpha proteins directly interacted with each other to a degree, in which Runt homology domain of Runx1 was mainly involved. Leukemia-related abnormal Runx1 fusion protein AML1-ETO, which fuses the N-terminal 177 amino acid residues of the Runx1 protein in frame to ETO (eight-twenty-one) protein, also interacted with HIF-1alpha protein with greater ability than Runx1 itself. More intriguingly, Runx1 overexpression inhibited DNA-binding and transcriptional activity of HIF-1 protein with reduced expression of HIF-1-targeted genes such as vascular endothelial growth factor, while silence of Runx1 expression by specific small interfering RNA significantly increased transcriptional activity of HIF-1 protein, suggesting that Runx1 inhibited transcription-dependent function of HIF-1. Vice versa, HIF-1alpha increased DNA-binding ability and transcriptional activity of Runx1 protein. All these data would shed new insight to understanding Runx1 and HIF-1alpha-related hematopoietic cell differentiation and angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • DNA / metabolism
  • Hematopoiesis / genetics
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neovascularization, Physiologic / genetics
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Transcription, Genetic*


  • Core Binding Factor Alpha 2 Subunit
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Small Interfering
  • DNA