Reactome | RUNX3 regulates CDKN1A transcription

RUNX3 regulates CDKN1A transcription

Stable Identifier

R-HSA-8941855

Type

Pathway

Species

Homo sapiens

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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).

Literature References

PubMed ID	Title	Journal	Year
16135801	RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD 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	Mol. Cell. Biol.	2005
20599712	Tumor suppressor, AT motif binding factor 1 (ATBF1), translocates to the nucleus with runt domain transcription factor 3 (RUNX3) in response to TGF-beta signal transduction 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	Biochem. Biophys. Res. Commun.	2010
20353948	RUNX3 modulates DNA damage-mediated phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53 Yamada, C, Ozaki, T, Ando, K, Suenaga, Y, Inoue, K, Ito, Y, Okoshi, R, Kageyama, H, Kimura, H, Miyazaki, M, Nakagawara, A	J. Biol. Chem.	2010