RUNX3 contributes to the upregulation of the CDKN1A (p21) gene transcription in response to TGF-beta (TGFB1) signaling. RUNX3 binds to SMAD3 and SMAD4, and cooperates with the activated SMAD3:SMAD4 complex in transactivation of CDKN1A. Runx3 knockout mice exhibit decreased sensitivity to TGF-beta and develop gastric epithelial hyperplasia (Chi et al. 2005). In response to TGF-beta signaling, the CBFB:RUNX3 complex binds to the tumor suppressor ZFHX3 (ATBF1) and, through an unknown mechanism, this complex positively regulates the CDKN1A transcription (Mabuchi et al. 2010).In addition, RUNX3 may act as a TP53 co-factor, stimulating TP53-mediated transcription of target genes, including CDKN1A (p21) (Yamada et al. 2010).
Chi, XZ, Yang, JO, Lee, KY, Ito, K, Sakakura, C, Li, QL, Kim, HR, Cha, EJ, Lee, YH, Kaneda, A, Ushijima, T, Kim, WJ, Ito, Y, Bae, SC
Mabuchi, M, Kataoka, H, Miura, Y, Kim, TS, Kawaguchi, M, Ebi, M, Tanaka, M, Mori, Y, Kubota, E, Mizushima, T, Shimura, T, Mizoshita, T, Tanida, S, Kamiya, T, Asai, K, Joh, T
Yamada, C, Ozaki, T, Ando, K, Suenaga, Y, Inoue, K, Ito, Y, Okoshi, R, Kageyama, H, Kimura, H, Miyazaki, M, Nakagawara, A
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