西亚试剂：Physical and functional interaction of Runt-related protein

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

Z G Peng1,4, M Y Zhou1,4, Y Huang2,3, J H Qiu3, L S Wang2, S H Liao1, S Dong3 and G Q Chen1,2

Correspondence: Professsor G-Q Chen, Department of Pathophysiology, Shanghai Jiaotong University School of Medicine, No. 280, Chong-Qing South Road, Shanghai 200025, China. E-mail: chengq@shsmu.edu.cn or gqchen@sibs.ac.cn

4These two authors contributed equally to this work.

Received 30 December 2006; Revised 23 April 2007; Accepted 18 June 2007; Published online 6 August 2007.

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