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

• Published in: Oncogene Vol. 27; no. 6; pp. 839 - 847
• Main Authors: Peng, Z G, Zhou, M Y, Huang, Y, Qiu, J H, Wang, L S, Liao, S H, Dong, S, Chen, G Q
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-01-2008; Nature Publishing; Nature Publishing Group
• Subjects: Acute myeloid leukemia; Amino acids; AML1 protein; Angiogenesis; Apoptosis; Biological and medical sciences; Cell Biology; Cell differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Deoxyribonucleic acid; DNA; DNA binding proteins; Fundamental and applied biological sciences. Psychology; Fusion protein; Genetic aspects; Health aspects; Homology; Human Genetics; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; Internal Medicine; Leukemia; Medicine; Medicine & Public Health; Molecular and cellular biology; Neovascularization; Oncology; original-article; Properties; Protein-protein interactions; Proteins; Runx1 protein; siRNA; Transcription factors; Vascular endothelial growth factor; China; protein–protein interaction; HIF-1; ); angiogenesis; hypoxia-inducible factor-1; runt-related protein 1 (Runx1); Angiogenesis; Oxygen; hypoxia-inducible factor-la (HIF-la); Hypoxia; Molecular interaction; protein-protein interaction; Carcinogenesis; runt- related protein 1 (Runxl); Protein
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210676

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
α
-subunit of angiogenesis-related hypoxia-inducible factor-1
α
(HIF-1
α
) 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-1
α
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-1
α
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-1
α
increased DNA-binding ability and transcriptional activity of Runx1 protein. All these data would shed new insight to understanding Runx1 and HIF-1
α
-related hematopoietic cell differentiation and angiogenesis.