title: The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice.
abstract: 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.
authors.affiliation: Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Harumi
authors.initials: H
authors.lastname: Yamamoto-Mukai
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Shimizu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Sou
authors.forename: Ayako
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shitara
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Chin Ha
authors.initials: CH
authors.lastname: Chung
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000235:genetics; D041905:Erythroid Cells; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011506:Proteins; C561795:Uba5 protein, mouse; C513664:Ufm1 protein, mouse; D044764:Ubiquitin-Activating Enzymes