title: E1-L2 activates both ubiquitin and FAT10.
abstract: Ubiquitination is catalyzed by a cascade of enzymes consisting of E1, E2, and E3. We report here the identification of an E1-like protein, termed E1-L2, that activates both ubiquitin and another ubiquitin-like protein, FAT10. Interestingly, E1-L2 can transfer ubiquitin to Ubc5 and Ubc13, but not Ubc3 and E2-25K, suggesting that E1-L2 may be specialized in a subset of ubiquitination reactions. E1-L2 forms a thioester with FAT10 in vitro, and this reaction requires the active-site cysteine of E1-L2 and the C-terminal diglycine motif of FAT10. Furthermore, endogenous FAT10 forms a thioester with E1-L2 in cells stimulated with tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma), which induce FAT10 expression. Silencing of E1-L2 expression by RNAi blocks the formation of FAT10 conjugates in cells. Deletion of E1-L2 in mice caused embryonic lethality, suggesting that E1-L2 plays an important role in embryogenesis.
authors: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors: Yu-Hsin
authors: YH
authors: Chiu
authors: Qinmiao
authors: Q
authors: Sun
authors: Zhijian J
authors: ZJ
authors: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020964:Embryo Loss / Q000201:enzymology; D047108:Embryonic Development; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D013438:Sulfhydryl Compounds / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000737:chemistry / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: C524073:E1-L2 protein, mouse; D013438:Sulfhydryl Compounds; C521757:UBA6 protein, human; C109184:UBD protein, human; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D044764:Ubiquitin-Activating Enzymes