Based on studies in mice, RUNX2 forms a complex with non-active (unphosphorylated) STAT1 in the cytosol. The interaction between the two proteins involves the DNA binding and linker domain of STAT1 and the Runt domain of RUNX2. Binding to STAT1 prevents translocation of RUNX2 to the nucleus and thus interferes with activation of RUNX2 target genes. STAT1 phosphorylation diminishes its interaction with RUNX2. Stat1 knockout mice exhibit increased bone mass and accelerated osteoblast differentiation, accompanied by enhnanced Runx2 activity (Kim et al. 2003).
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