The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice.
The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice.
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DOI：
10.1038/ncomms1182
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发表时间：
2011-02-08
影响因子：
16.6
通讯作者：
Komatsu M
中科院分区：
文献类型：
--
作者：
Tatsumi K;Yamamoto-Mukai H;Shimizu R;Waguri S;Sou YS;Sakamoto A;Taya C;Shitara H;Hara T;Chung CH;Tanaka K;Yamamoto M;Komatsu M
翻译后蛋白质修饰是设计用于通过靶分子的功能转换来扩展受限基因组信息的系统。泛素样翻译后修饰物通过其与靶蛋白的共价连接，通过类似于由E1（活化）、E2（缀合）和E3（连接）酶组成的泛素化的酶级联反应调节许多细胞事件。在这项研究中，我们报告的Uba5，一个特定的活化酶的泛素样修饰剂，Ufm1，在红细胞发育的重要作用。缺乏Uba5的小鼠表现出严重的贫血，随后在子宫内死亡。虽然Uba5是一个产生促红细胞生成素的基因，但它的遗传缺失导致从普通髓系祖细胞向巨核细胞和红系祖细胞的发育受损。有趣的是，转基因表达的Uba5在红细胞系拯救了Uba5缺陷的胚胎贫血和延长他们的生存，证明了Uba5在细胞自主红细胞分化的重要性。我们的研究结果表明，泛素样蛋白修饰系统之一，Ufm1系统，参与造血的调节。 翻译后修饰在调节蛋白质功能和周转中是重要的，并且Ufm1是最近鉴定的蛋白质修饰系统的一部分。在这项研究中，作者表明Uba5是Ufm1系统的一个组成部分，对调节造血和红系细胞的分化很重要。
Post-translational protein modifications are systems designed to expand restricted genomic information through functional conversion of target molecules. Ubiquitin-like post-translational modifiers regulate numerous cellular events through their covalent linkages to target protein(s) by an enzymatic cascade analogous to ubiquitylation consisting of E1 (activating), E2 (conjugating) and E3 (ligating) enzymes. In this study, we report the essential role of Uba5, a specific activating enzyme for the ubiquitin-like modifier, Ufm1, in erythroid development. Mice lacking Uba5 exhibited severe anaemia, followed by death in utero. Although Uba5 was dispensable for the production of erythropoietin, its genetic loss led to impaired development of megakaryocyte and erythroid progenitors from common myeloid progenitors. Intriguingly, transgenic expression of Uba5 in the erythroid lineage rescued the Uba5-deficient embryos from anaemia and prolonged their survival, demonstrating the importance of Uba5 in cell-autonomous erythroid differentiation. Our results suggest that one of the ubiquitin-like protein modification systems, the Ufm1 system, is involved in the regulation of haematopoiesis. Post-translational modifications are important in regulating protein function and turnover, and Ufm1 is part of a recently identified protein modification system. In this study, the authors show that Uba5, a component of the Ufm1 system, is important for regulating haematopoiesis and the differentiation of erythroid cells.
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影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
20.3
作者：
Zhang, Ji;Randall, Mindy S.;Ney, Paul A.
通讯作者：
Ney, Paul A.
影响因子：
11.4
作者：
Komatsu, M;Chiba, T;Tanaka, K
通讯作者：
Tanaka, K
DOI：
10.1073/pnas.94.9.4487
发表时间：
1997-04-29
影响因子：
11.1
作者：
Onodera, K;Takahashi, S;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
16
作者：
Chiu, Yu-Hsin;Sun, Qinmiao;Chen, Zhijian J.
通讯作者：
Chen, Zhijian J.