The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex.
The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex.
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DOI：
10.1371/journal.pone.0051331
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Winkler GS
中科院分区：
文献类型：
--
作者：
Doidge R;Mittal S;Aslam A;Winkler GS
人类BTG/TOB蛋白家族包括6个成员（BTG1, BTG2/PC3/Tis21, BTG3/Ana, BTG4/PC3B， TOB1/ TOB和TOB2），其特征是一个保守的BTG结构域。该结构域介导与高度相似的Ccr4-Not deadenylase复合物的Caf1a （CNOT7）和Caf1b （CNOT8）催化亚基的相互作用。BTG/TOB蛋白具有抗增殖活性：敲低BTG/TOB可导致细胞增殖增加，而过表达BTG/TOB可抑制细胞周期进程。目前尚不清楚BTG/TOB蛋白与Caf1a/Caf1b死烯酶之间的相互作用是否是BTG/TOB抗增殖活性的必要条件。为了解决这个问题，我们进一步表征了BTG2和TOB1表面暴露的氨基酸残基，这些氨基酸残基介导了与Caf1a和Caf1b死基酶的相互作用。然后，我们分析了BTG2和TOB1在调节细胞增殖、翻译和mRNA丰度中的作用，使用不再能够与Caf1a/Caf1b死酶相互作用的突变体。我们得出结论，BTG/TOB蛋白的抗增殖活性是通过与Caf1a和Caf1b deadenylase酶的相互作用介导的。此外，我们发现BTG/TOB蛋白在mRNA丰度和翻译调控中的活性依赖于Caf1a/Caf1b，并且似乎不需要其他Ccr4-Not组分，包括Ccr4a (CNOT6)/Ccr4b （CNOT6L）死基酶，或非催化亚基CNOT1或CNOT3。
The human BTG/TOB protein family comprises six members (BTG1, BTG2/PC3/Tis21, BTG3/Ana, BTG4/PC3B, TOB1/Tob, and TOB2) that are characterised by a conserved BTG domain. This domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deadenylase complex. BTG/TOB proteins have anti-proliferative activity: knockdown of BTG/TOB can result in increased cell proliferation, whereas over-expression of BTG/TOB leads to inhibition of cell cycle progression. It was unclear whether the interaction between BTG/TOB proteins and the Caf1a/Caf1b deadenylases is necessary for the anti-proliferative activity of BTG/TOB. To address this question, we further characterised surface-exposed amino acid residues of BTG2 and TOB1 that mediate the interaction with the Caf1a and Caf1b deadenylase enzymes. We then analysed the role of BTG2 and TOB1 in the regulation of cell proliferation, translation and mRNA abundance using a mutant that is no longer able to interact with the Caf1a/Caf1b deadenylases. We conclude that the anti-proliferative activity of BTG/TOB proteins is mediated through interactions with the Caf1a and Caf1b deadenylase enzymes. Furthermore, we show that the activity of BTG/TOB proteins in the regulation of mRNA abundance and translation is dependent on Caf1a/Caf1b, and does not appear to require other Ccr4-Not components, including the Ccr4a (CNOT6)/Ccr4b (CNOT6L) deadenylases, or the non-catalytic subunits CNOT1 or CNOT3.
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影响因子：
9.7
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通讯作者：
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