Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis.
Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis.
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DOI：
10.1093/nar/gkw790
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发表时间：
2016-11-16
影响因子：
14.9
通讯作者：
Kutay U
中科院分区：
文献类型：
--
作者：
Bammert L;Jonas S;Ungricht R;Kutay U
哺乳动物AATF/Che-1对胚胎发育至关重要，但其潜在的分子机制尚不清楚。通过对人AATF的免疫沉淀，我们发现AATF与神经导向蛋白（NGDN）和NOL 10形成盐稳定的蛋白复合物，并证明AATF-NGDN-NOL 10（ANN）复合物在核糖体生物合成中起作用。所有三个人工神经网络复杂的成员本地化的核仁，并显示相互依赖的蛋白质稳定性。蛋白质-蛋白质相互作用结构域的定位揭示了NOL 10中进化保守的WD 40重复序列和NGDN中的UTP 3/SAS 10结构域对于复合物形成的重要性。功能分析表明，人工神经网络复合物支持40 S核糖体亚基生物合成的核仁步骤。所有复合体成员都是18 S rRNA成熟所必需的，它们各自的缺失影响核糖体RNA前体5′ETS和ITS 1区相同的核仁切割步骤。总的来说，我们确定了人工神经网络复合物作为一种新的功能模块，支持40 S核糖体亚基的核仁成熟。我们的数据有助于解释AATF在小鼠发育过程中细胞增殖中的作用，以及其对恶性肿瘤生长的要求。
Mammalian AATF/Che-1 is essential for embryonic development, however, the underlying molecular mechanism is unclear. By immunoprecipitation of human AATF we discovered that AATF forms a salt-stable protein complex together with neuroguidin (NGDN) and NOL10, and demonstrate that the AATF-NGDN-NOL10 (ANN) complex functions in ribosome biogenesis. All three ANN complex members localize to nucleoli and display a mutual dependence with respect to protein stability. Mapping of protein-protein interaction domains revealed the importance of both the evolutionary conserved WD40 repeats in NOL10 and the UTP3/SAS10 domain in NGDN for complex formation. Functional analysis showed that the ANN complex supports nucleolar steps of 40S ribosomal subunit biosynthesis. All complex members were required for 18S rRNA maturation and their individual depletion affected the same nucleolar cleavage steps in the 5′ETS and ITS1 regions of the ribosomal RNA precursor. Collectively, we identified the ANN complex as a novel functional module supporting the nucleolar maturation of 40S ribosomal subunits. Our data help to explain the described role of AATF in cell proliferation during mouse development as well as its requirement for malignant tumor growth.
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影响因子：
7.3
作者：
Henras, Anthony K.;Plisson-Chastang, Celia;O'Donohue, Marie-Francoise;Chakraborty, Anirban;Gleizes, Pierre-Emmanuel
通讯作者：
Gleizes, Pierre-Emmanuel
影响因子：
4.8
作者：
Fanciulli, M;Bruno, T;Passananti, C
通讯作者：
Passananti, C
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
4.8
作者：
Guo, Q;Xie, J
通讯作者：
Xie, J
DOI：
10.1016/j.str.2009.07.014
发表时间：
2009-09-09
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Brohawn SG;Partridge JR;Whittle JR;Schwartz TU
通讯作者：
Schwartz TU