Urm1 couples sulfur transfer to ubiquitin-like protein function in oxidative stress: Fig. 1.

Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2011; 108(5):1749-50. DOI: 10.1073/pnas.1019043108
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Available from: Dieter A. Wolf, Aug 13, 2014
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    • "The biological significance of this process, however, remains to be determined [6,9]. The apparent conservation of the machinery involved in sulfur transfer and protein conjugation suggests an evolutionary relationship between these systems [10]. An additional, interesting aspect of loci involved in tRNA thiolation is that they frequently have been identified as modifiers of the TOR (Target of Rapamycin) network [11,12], a major controller of cell growth in eukaryotes [13]. "
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    ABSTRACT: A large number of post-transcriptional modifications of transfer RNAs (tRNAs) have been described in prokaryotes and eukaryotes. They are known to influence their stability, turnover, and chemical/physical properties. A specific subset of tRNAs contains a thiolated uridine residue at the wobble position to improve the codon-anticodon interaction and translational accuracy. The proteins involved in tRNA thiolation are reminiscent of prokaryotic sulfur transfer reactions and of the ubiquitylation process in eukaryotes. In plants, some of the proteins involved in this process have been identified and show a high degree of homology to their non-plant equivalents. For other proteins, the identification of the plant homologs is much less clear, due to the low conservation in protein sequence. This manuscript describes the identification of CTU2, the second CYTOPLASMIC THIOURIDYLASE protein of Arabidopsis thaliana. CTU2 is essential for tRNA thiolation and interacts with ROL5, the previously identified CTU1 homolog of Arabidopsis. CTU2 is ubiquitously expressed, yet its activity seems to be particularly important in root tissue. A ctu2 knock-out mutant shows an alteration in root development. The analysis of CTU2 adds a new component to the so far characterized protein network involved in tRNA thiolation in Arabidopsis. CTU2 is essential for tRNA thiolation as a ctu2 mutant fails to perform this tRNA modification. The identified Arabidopsis CTU2 is the first CTU2-type protein from plants to be experimentally verified, which is important considering the limited conservation of these proteins between plant and non-plant species. Based on the Arabidopsis protein sequence, CTU2-type proteins of other plant species can now be readily identified.
    Full-text · Article · Apr 2014 · BMC Plant Biology
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    • "Based on observations, Urm1 does not appear to have a role in targeting proteins for degradation, and no polyurmylation has been detected. Why its E1 MOCS3, two deubiquitinating enzymes, CAS, and some other important enzymes are modified still remains unclear, because no change was found in the activity of these enzymes after Urm1 conjugation (Petroski et al., 2011; Van der Veen et al., 2011). Although these questions remain unanswered, we now clearly know that Urm1 is an important protein modifier that shares similar features with both sulfur carriers and UBLs. "
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    ABSTRACT: The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine residues of other proteins, such as yeast Ahp1 and human MOCS3, through a mechanism involving the E1-like protein Uba4 (MOCS3 in humans). Similar to ubiquitination, urmylation requires a thioester intermediate and forms isopeptide bonds between Urm1 and its substrates. In addition, the urmylation process can be significantly enhanced by oxidative stress. Recent findings have demonstrated that Urm1 also acts as a sulfur carrier in the thiolation of eukaryotic tRNA via a mechanism that requires the formation of a thiocarboxylated Urm1. This role is very similar to that of prokaryotic sulfur carriers such as MoaD and ThiS. Evidence strongly supports the hypothesis that Urm1 is the molecular fossil in the evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins. In the present review, we discuss the dual role of Urm1 in protein and tRNA modification.
    Full-text · Article · Aug 2011 · Protein & Cell
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    ABSTRACT: Signaling networks for ubiquitin and ubiquitin-like proteins bymass spectrometry are discussed and site-specific studies published in 2010 and 2011 are presented. This the field is aiming to develop novel methods to identify these modifications in a site-specific manner. Systematic, unbiased, and proteome-wide studies on protein ubiquitylation and UBL conjugation will strongly improve our understanding of these modifications in the near future, particularly with respect to the identification of target proteins for the vast numbers of ligases and proteases in the system and to identify the targets that are dynamically regulated in response to a wide variety of stimuli. This is furthermore relevant for the detailed understanding of deregulation of ubiquitin signaling in human diseases and for the development of drugs that target components of ubiquitin signaling cascades.
    Preview · Article · Dec 2011 · Chemical Reviews
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