TY - JOUR
T1 - The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice
AU - Tatsumi, Kanako
AU - Yamamoto-Mukai, Harumi
AU - Shimizu, Ritsuko
AU - Waguri, Satoshi
AU - Sou, Yu Shin
AU - Sakamoto, Ayako
AU - Taya, Choji
AU - Shitara, Hiroshi
AU - Hara, Takahiko
AU - Chung, Chin Ha
AU - Tanaka, Keiji
AU - Yamamoto, Masayuki
AU - Komatsu, Masaaki
N1 - Funding Information:
We thank T. Kouno (Tokyo Metropolitan Institute of Medical Science) and Y. Kawatani (Tohoku University Graduate School of Medicine) for their technical assistance. We also thank A. Yamada, K. Kanno and A. Yabashi (Fukushima Medical University School of Medicine) for their help with histological studies. This work was supported by grants from the Japan Science and Technology Agency (M.K.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.K., K.T. and M.Y.) and the Tohoku University Global COE Program from JSPS (M.Y.). K.T. and Y.-S.S. were supported by the Japan Society for the Promotion of Science.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms1182
DO - 10.1038/ncomms1182
M3 - Article
C2 - 21304510
AN - SCOPUS:84880278483
VL - 2
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 181
ER -