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

Abstract

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.

• Authors: Z G Peng, M Y Zhou, Y Huang, J H Qiu, L S Wang, S H Liao, S Dong, G Q Chen
• Journal: Oncogene (Oncogene) Vol. 27 Issue 6 Pg. 839-47 (Jan 31 2008) ISSN: 1476-5594 [Electronic] England
• PMID: 17684492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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