Article

E1-L2 activates both ubiquitin and FAT10

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Molecular Cell (Impact Factor: 14.46). 10/2007; 27(6):1014-23. DOI: 10.1016/j.molcel.2007.08.020
Source: PubMed

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.

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    • "To avoid confusion in terminology, we respectively refer to these two isoforms as Uba1A, defined here as the predominantly nuclear form of Uba1, and Uba1B, defined here as the cytoplasmic form of Uba1, instead of E1a and E1b. Uba6 is required to activate the E2 Use1 (Uba6-specific E2) both in vitro and in vivo [6] and can also activate another ubiquitin-like modifier, FAT10 [7]. "
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    PLoS ONE 05/2014; 9(5):e96666. DOI:10.1371/journal.pone.0096666 · 3.23 Impact Factor
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    • "Thus FAT10, the FAT10-binding adapter molecule Nub1 and its recently reported E1 enzyme UBE1L2 that also activates Ub belong to the few genes found to be induced under all four stimulation strategies used in this study (Figs. 2 and 4). In agreement with studies reporting the rapid proteasome dependent degradation of FAT10 conjugates in target cells (Chiu et al., 2007), accumulated FAT10-conjugates were stabilized by proteasome inhibition (Fig. 4). No obvious histological differences were found in FAT10 deficient mice (Hipp et al., 2004, 2005). "
    Dataset: Ebstein2009
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    • "EVI2A is an uncharacterized factor not included in the IPA network with blood-specific expression [42]. Cluster 7 members regulate a range of cellular mechanisms, including protein recycling [94], signal transduction [95], immuno-modulation [92], and transcript maturation [96]. "
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