Antiproliferative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB
Antiproliferative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB
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DOI：
10.1038/onc.2012.548
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发表时间：
2014-01-01
期刊：
影响因子：
8
通讯作者：
Hoshino, S.
中科院分区：
文献类型：
--
作者：
Ogami, K.;Hosoda, N.;Hoshino, S.
mRNA去腺苷化的调控是基因表达转录后调控的重要机制。在这里，我们表明，抗增殖蛋白Tob，Caf 1-Ccr 4去腺苷酶复合物的一个组成部分，参与调节原癌基因c-myc的表达。c-myc mRNA在其3 '-非翻译区（3'-UTR）含有顺式元件（CPE），其被胞质多聚腺苷酸化元件结合蛋白（CPEB）识别。CPEB通过与Tob相互作用招募Caf 1去腺苷酶，形成三元复合物CPEB-Tob-Caf 1，并通过加速其mRNA的去腺苷化和衰变来负调节c-myc的表达。在静止期细胞中，c-myc mRNA被反式作用复合物（CPEB-Tob-Caf 1）破坏稳定，而在血清刺激的细胞中，Tob和Caf 1都从CPEB中释放出来，c-Myc表达在刺激后早期通过其mRNA作为“立即早期基因”的稳定性诱导。总的来说，这些结果表明，Tob是一个关键因素的c-myc基因的表达，这是必不可少的细胞生长的调节。因此，Tob似乎至少部分地通过调节c-myc的表达来控制细胞生长。
The regulation of mRNA deadenylation constitutes a pivotal mechanism of the post-transcriptional control of gene expression. Here we show that the antiproliferative protein Tob, a component of the Caf1-Ccr4 deadenylase complex, is involved in regulating the expression of the proto-oncogene c-myc. The c-myc mRNA contains cis elements (CPEs) in its 3'-untranslated region (3'-UTR), which are recognized by the cytoplasmic polyadenylation element-binding protein (CPEB). CPEB recruits Caf1 deadenylase through interaction with Tob to form a ternary complex, CPEB-Tob-Caf1, and negatively regulates the expression of c-myc by accelerating the deadenylation and decay of its mRNA. In quiescent cells, c-myc mRNA is destabilized by the trans-acting complex (CPEB-Tob-Caf1), while in cells stimulated by the serum, both Tob and Caf1 are released from CPEB, and c-Myc expression is induced early after stimulation by the stabilization of its mRNA as an 'immediate-early gene'. Collectively, these results indicate that Tob is a key factor in the regulation of c-myc gene expression, which is essential for cell growth. Thus, Tob appears to function in the control of cell growth at least, in part, by regulating the expression of c-myc.