Article

A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway.

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Proceedings of the National Academy of Sciences (impact factor: 9.68). 12/2008; 105(47):18255-60. DOI:10.1073/pnas.0808756105 pp.18255-60
Source: PubMed

ABSTRACT Urm1 is a highly conserved ubiquitin-related modifier of unknown function. A reduction of cellular Urm1 levels causes severe cytokinesis defects in HeLa cells, resulting in the accumulation of enlarged multinucleated cells. To understand the underlying mechanism, we applied a functional proteomics approach and discovered an enzymatic activity that links Urm1 to a tRNA modification pathway. Unlike ubiquitin (Ub) and many Ub-like modifiers, which are commonly conjugated to proteinaceous targets, Urm1 is activated by an unusual mechanism to yield a thiocarboxylate intermediate that serves as sulfur donor in tRNA thiolation reactions. This mechanism is reminiscent of that used by prokaryotic sulfur carriers and thus defines the evolutionary link between ancient Ub progenitors and the eukaryotic Ub/Ub-like modification systems.

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    Article: Modification of proteins by ubiquitin and ubiquitin-like proteins.
    Oliver Kerscher, Rachael Felberbaum, Mark Hochstrasser
    [show abstract] [hide abstract]
    ABSTRACT: Following the discovery of protein modification by the small, highly conserved ubiquitin polypeptide, a number of distinct ubiquitin-like proteins (Ubls) have been found to function as protein modifiers as well. These Ubls, which include SUMO, ISG15, Nedd8, and Atg8, function as critical regulators of many cellular processes, including transcription, DNA repair, signal transduction, autophagy, and cell-cycle control. A growing body of data also implicates the dysregulation of Ubl-substrate modification and mutations in the Ubl-conjugation machinery in the etiology and progression of a number of human diseases. The primary aim of this review is to summarize the latest developments in our understanding of the different Ubl-protein modification systems, including the shared and unique features of these related pathways.
    Annual Review of Cell and Developmental Biology 02/2006; 22:159-80. · 15.84 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

accumulation
 
ancient Ub progenitors
 
cellular Urm1 levels causes severe cytokinesis defects
 
conserved ubiquitin-related modifier
 
evolutionary link
 
functional proteomics approach
 
links Urm1
 
prokaryotic sulfur carriers
 
sulfur donor
 
thiocarboxylate intermediate
 
tRNA modification pathway
 
tRNA thiolation reactions
 
underlying mechanism
 
unusual mechanism
 
Urm1
 

Christian D Schlieker