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

Oncogene volume 27, pages 839–847 (2008)Cite this article

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

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Acknowledgements

We thank Dr SW Hiebert, Dr Y Fujii-Kuriyama and Dr DE Zhang for generously providing plasmids. We are also grateful to Dr AS Belmont (University of Illinois Champagne-Urbana) and Dr M Mancini (Baylor College of Medicine) for kindly providing the A03_1 cell line, sharing reagents and for assistance in developing and interpreting the LacO array experiments. This work was supported by grants from National Key Program (973) for Basic Research of China (NO2002CB512805), National Natural Science Foundation of China (30630034; 30500215) and grants from Science and Technology Commission of Shanghai (05JC14032) and Chinese Academy of Science. Dr GQ Chen is a Chang Jiang Scholar of Ministry of Education of People's Republic of China, and is supported by Shanghai Ling-Jun Talent Program.

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Author notes

  1. Z G Peng and M Y Zhou: These two authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Health Science, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences-Shanghai Jiao-Tong University School of Medicine (SJTU-SM, formerly Shanghai Second Medical University), Shanghai, China

    Z G Peng, M Y Zhou, S H Liao & G Q Chen

  2. Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China

    Y Huang, L S Wang & G Q Chen

  3. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Y Huang, J H Qiu & S Dong

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  1. Z G Peng
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Correspondence to G Q Chen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Peng, Z., Zhou, M., Huang, Y. et al. Physical and functional interaction of Runt-related protein 1 with hypoxia-inducible factor-1α. Oncogene 27, 839–847 (2008). https://doi.org/10.1038/sj.onc.1210676

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