RUNX3 binds the complex of SMAD4 and SMAD3, generated in response to TGF-beta (TGFB1) signaling. While the individual action of the SMAD3:SMAD4 complex or RUNX3 can induce 2-3-fold activation of CDKN1A transcription, the synergistic action of SMAD3, SMAD4 and RUNX3 induces 10-fold activation of CDKN1A transcription. Runx3 knockout mice exhibit decreased sensitivity to TGF-beta and develop gastric epithelial hyperplasia (Chi et al. 2005).
Sakakura, C, Lee, YH, Ito, K, Bae, SC, Ito, Y, Cha, EJ, Chi, XZ, Kaneda, A, Ushijima, T, Li, QL, Lee, KY, Kim, HR, Yang, JO, Kim, WJ
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