Reactome | CDKN1A gene expression is synergistically activated by RUNX3, SMAD3 and SMAD4

CDKN1A gene expression is synergistically activated by RUNX3, SMAD3 and SMAD4

Stable Identifier

R-HSA-8878186

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

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CDKN1A gene expression is synergistically activated by RUNX3, SMAD3 and SMAD4

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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).

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