Physical and Functional Interactions between STAT5 and Runx Transcription Factors

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.