The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice

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...

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Published inNature communications Vol. 2; no. 1; p. 181
Main Authors Yamamoto, Masayuki, Komatsu, Masaaki, Tatsumi, Kanako, Yamamoto-Mukai, Harumi, Shimizu, Ritsuko, Waguri, Satoshi, Sou, Yu-Shin, Sakamoto, Ayako, Taya, Choji, Shitara, Hiroshi, Hara, Takahiko, Chung, Chin Ha, Tanaka, Keiji
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 08.02.2011
Nature Publishing Group
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Summary: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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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms1182