Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex
Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex
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DOI：
10.1111/j.1349-7006.2008.00746.x
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发表时间：
2008-04-01
期刊：
影响因子：
5.7
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Miyasaka, Takashi;Morita, Masahiro;Yamamoto, Tadashi
Tob蛋白，当过表达时，抑制NIH 3 T3细胞的生长，推测是通过调节各种生长相关基因的表达。然而，潜在的Tob-mediated基因表达调控的分子机制一直是模糊的。为了解决这个问题，我们建立了稳定的Tob-expressing细胞系，并使用蛋白质组学的方法来确定Tob-interacting蛋白。我们发现Tob与CCR 4-NOT复合物相关。Tob的羧基末端的一半与CCR 4-NOT复合物的核心蛋白Cnot 1相互作用。我们进一步表明，与复合物相关的去腺苷酶活性在体外被Tob抑制。这些结果表明，Tob的抗增殖活性是通过控制靶mRNA的稳定性在转录后显示的，除了它参与转录调控，以前报道。
Tob protein, when overexpressed, suppresses growth of NIH3T3 cells, presumably by regulating expression of various growth-related genes. However, the molecular mechanisms underlying Tob-mediated regulation of gene expression have been obscure. To address this issue we established stable Tob-expressing cell lines and used a proteomics approach to identify Tob-interacting proteins. We found that Tob associates with the CCR4-NOT complex. The carboxyl-terminal half of Tob interacted with Cnot1, a core protein of the CCR4-NOT complex. We further showed that the deadenylase activity associated with the complex was suppressed in vitro by Tob. These results suggest that the antiproliferative activity of Tob is shown post-transcriptionally by controlling the stability of the target mRNAs in addition to its involvement in transcriptional regulation, reported previously.