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 ...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.展开更多
文摘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.
