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Journal of Biochemistry Advance Access originally published online on February 22, 2008
Journal of Biochemistry 2008 143(5):695-709; doi:10.1093/jb/mvn022
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© 2008 The Japanese Biochemical Society.

Physical and Functional Interactions between STAT5 and Runx Transcription Factors

Shinya Ogawa1,2, Masanobu Satake3 and Koichi Ikuta1,*

1Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507; 2Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501; and 3Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan

*To whom correspondence should be addressed. Tel: +81-75-751-4012, Fax: +81-75-751-4810, E-mail: ikuta{at}virus.kyoto-u.ac.jp

Received January 31, 2008; Accepted February 11, 2008


  Abstract

The signal transducers and activators of transcription (STAT) and the Runt-related (Runx) are two of major transcription factor families that play essential roles in lymphocyte development. Although the interaction of Runx2 with STAT1 and STAT3 has been reported before, the interaction between STAT5 and Runx family proteins has not been characterized. In this study, we first showed that STAT5 physically interacts with Runx1, Runx2 and Runx3 by co-immunoprecipitation experiments. The Runt domain of Runx proteins and the DNA-binding domain and {alpha}-helix loop structure of STAT5 are responsible for the interaction. When expressed in CHO cells, STAT5 inhibits the nuclear localization of Runx proteins and retains them in the cytoplasm. In addition, we showed by reporter assay that the interaction between STAT5 and Runx proteins mutually inhibits their transcriptional activity. Furthermore, Runx proteins inhibit the DNA-binding activity of STAT5. Finally, we found that Runx proteins suppress the transcription of an endogenous STAT5 target gene, cytokine-inducible SH2 protein-1, in an interleukin-3-dependent pro-B cell line, Ba/F3. These results collectively suggested that STAT5 and Runx proteins physically and functionally interact to mutually inhibit their transcriptional activity. Thus, this study implies a potential role of the STAT5–Runx interaction in lymphocyte development.

Key Words: interleukin-7, Runx, signal transduction, STAT5, transcription factor

Abbreviations: CA, constitutively active; ChIP, chromatin immunoprecipitation; CIS1, cytokine-inducible SH2 protein-1; DAPI, 4, 6-dia-midino-2-phenylindole; EMSA, electrophoretic mobility shift assay; hnRNP, heterogeneous nuclear ribonucleoprotein; IL, interleukin; PABP, poly(A)-binding protein; Runx, Runt-related; SH2, Src homology 2; STAT, signal transducers and activators of transcription; WT, wild type


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