From the Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China and.
J Biol Chem. 2014 Jan 24;289(4):2072-83. doi: 10.1074/jbc.M113.526905. Epub 2013 Dec 9.
ZNF451 is a transcriptional cofactor localized to promyelocytic leukemia bodies. Here, we present evidence demonstrating that ZNF451 physically interacts with Smad3/4 and functionally inhibits TGF-β signaling. Increased expression of ZNF451 attenuates TGF-β-induced growth inhibitory and gene transcriptional responses, whereas depletion of ZNF451 enhances TGF-β responses. Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response to TGF-β, which causes reduction of histone H3K9 acetylation on the promoters of TGF-β target genes. Taken together, ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-β signaling.
ZNF451 是一种转录共激活因子，定位于早幼粒细胞白血病小体。在这里，我们提供了证据表明 ZNF451 与 Smad3/4 相互作用，并在功能上抑制 TGF-β 信号通路。ZNF451 的表达增加可减弱 TGF-β 诱导的生长抑制和基因转录反应，而 ZNF451 的缺失则增强 TGF-β 反应。从机制上讲，ZNF451 阻止 Smad3/4 在 TGF-β 作用下募集 p300 的能力，从而导致 TGF-β 靶基因启动子上组蛋白 H3K9 乙酰化减少。综上所述，ZNF451 作为 Smad3/4 的转录共抑制因子，负调控 TGF-β 信号通路。
