RUNX3 regulates CDKN1A transcription

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).<br>In addition, RUNX3 may act as a TP53 co-factor, stimulating TP53-mediated transcription of target genes, including CDKN1A (p21) (Yamada et al. 2010).

RUNX3基因在TGF-β（TGFB1）信号传导的刺激下，对CDKN1A（p21）基因的转录上调起到重要作用。RUNX3与SMAD3和SMAD4结合，并与激活的SMAD3:SMAD4复合物协同，促进CDKN1A的转录激活。Runx3敲除小鼠对TGF-β的敏感性降低，并发生胃上皮细胞增生（Chi等，2005年）。在TGF-β信号传导的响应中，CBFB:RUNX3复合物与肿瘤抑制因子ZFHX3（ATBF1）结合，通过一种未知的机制，此复合物正向调控CDKN1A的转录（Mabuchi等，2010年）。此外，RUNX3可能作为TP53的共因子，刺激TP53介导的目标基因转录，包括CDKN1A（p21）（Yamada等，2010年）。