Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity.

Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity.
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参与抑制 CAF1 去腺苷酶活性的人 BTG2 和小鼠 TIS21 的晶体结构

DOI:
10.1093/nar/gkn825
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发表时间:
2008-12
影响因子:
14.9
通讯作者:
Rao Z
Rao Z
中科院分区:
生物学2区
文献类型:
--
作者:
Yang X;Morita M;Wang H;Suzuki T;Yang W;Luo Y;Zhao C;Yu Y;Bartlam M;Yamamoto T;Rao Z

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BTG 2是TOB家族的原型成员,已知参与细胞生长、分化和DNA修复。作为转录共调节因子,BTG 2与CCR 4相关因子1(CAF 1)和POP 2(CALIF)相互作用,这是一般CCR 4/NOT多亚基转录复合物的关键组分,并且据报道作为参与mRNA去腺苷化的核酸酶发挥不同的作用。在这里,我们报告的晶体结构的人BTG 2和小鼠TIS 21的分辨率分别为2.3 μ m和2.2 μ m。结构揭示了推定的CAF 1结合位点。用野生型BTG 2和破坏与CAF 1相互作用的突变体进行CAF 1去腺苷酶测定。结果揭示了BTG 2在调节CAF 1去腺苷酶活性中的抑制作用。我们的研究为BTG 2-CAF 1复合物的形成以及BTG 2在CAF 1调节中的潜在作用提供了见解。
BTG2 is the prototypical member of the TOB family and is known to be involved in cell growth, differentiation and DNA repair. As a transcriptional co-regulator, BTG2 interacts with CCR4-associated factor 1 (CAF1) and POP2 (CALIF), which are key components of the general CCR4/NOT multi-subunit transcription complex, and which are reported to play distinct roles as nucleases involved in mRNA deadenylation. Here we report the crystal structures of human BTG2 and mouse TIS21 to 2.3 Å and 2.2 Å resolution, respectively. The structures reveal the putative CAF1 binding site. CAF1 deadenylase assays were performed with wild-type BTG2 and mutants that disrupt the interaction with CAF1. The results reveal the suppressive role of BTG2 in the regulation of CAF1 deadenylase activity. Our study provides insights into the formation of the BTG2-CAF1 complex and the potential role of BTG2 in the regulation of CAF1.
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