Transforming growth factor-β stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation
Transforming growth factor-β stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation
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DOI：
10.1074/jbc.m313120200
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发表时间：
2004-07-09
影响因子：
4.8
通讯作者：
Bae, SC
中科院分区：
文献类型：
--
作者：
Jin, YH;Jeon, EJ;Bae, SC
Runt结构域转录因子（RUNXs）在正常发育和肿瘤发生中起着重要作用。动物和人类的遗传分析表明，RUNX1参与造血和白血病，RUNX2参与骨形成和锁骨颅发育不良，RUNX3参与t细胞和背根神经节神经元的发育以及胃癌的发生。这里我们报道RUNX3是p300乙酰转移酶活性的靶标。三个赖氨酸残基的p300依赖性乙酰化保护RUNX3免受泛素连接酶smurf介导的降解。乙酰化程度受转化生长因子- β信号通路的上调和组蛋白去乙酰化酶活性的下调。我们的研究结果表明，RUNX3蛋白水平受三个赖氨酸残基的竞争性乙酰化和去乙酰化控制，揭示了RUNX3翻译后表达调控的新机制。
The Runt domain transcription factors (RUNXs) play essential roles in normal development and neoplasias. Genetic analyses of animals and humans have revealed the involvement of RUNX1 in hematopoiesis and leukemia, RUNX2 in osteogenesis and cleidocranial dysplasia, and RUNX3 in the development of T-cells and dorsal root ganglion neurons and in the genesis of gastric cancer. Here we report that RUNX3 is a target of the acetyltransferase activity of p300. The p300-dependent acetylation of three lysine residues protects RUNX3 from ubiquitin ligase Smurf-mediated degradation. The extent of the acetylation is up-regulated by the transforming growth factor-beta signaling pathway and down-regulated by histone deacetylase activities. Our findings demonstrate that the level of RUNX3 protein is controlled by the competitive acetylation and deacetylation of the three lysine residues, revealing a new mechanism for the posttranslational regulation of RUNX3 expression.