Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifier
- 5 January 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 108 (5), 1763-1770
- https://doi.org/10.1073/pnas.1014402108
Abstract
The ubiquitin (Ub)-related modifier Urm1 functions as a sulfur carrier in tRNA thiolation by means of a mechanism that requires the formation of a thiocarboxylate at the C-terminal glycine residue of Urm1. However, whether Urm1 plays an additional role as a Ub-like protein modifier remains unclear. Here, we show that Urm1 is conjugated to lysine residues of target proteins and that oxidative stress enhances protein urmylation in both Saccharomyces cerevisiae and mammalian cells. Similar to ubiquitylation, urmylation involves a thioester intermediate and results in the formation of a covalent peptide bond between Urm1 and its substrates. In contrast to modification by canonical Ub-like modifiers, however, conjugation of Urm1 involves a C-terminal thiocarboxylate of the modifier. We have confirmed that the peroxiredoxin Ahp1 is such a substrate in S. cerevisiae and found that Urm1 targets a specific lysine residue of Ahp1 in vivo. In addition, we have identified several unique substrates in mammalian cells and show that Urm1 targets at least two pathways on oxidant treatment. First, Urm1 is appended to lysine residues of three components that function in its own pathway (i.e., MOCS3, ATPBD3, and CTU2). Second, Urm1 is conjugated to the nucleocytoplasmic shuttling factor cellular apoptosis susceptibility protein. Thus, Urm1 has a conserved dual role by integrating the functions of prokaryotic sulfur carriers with those of eukaryotic protein modifiers of the Ub family.Keywords
This publication has 40 references indexed in Scilit:
- Urmylation: A Ubiquitin-like Pathway that Functions during Invasive Growth and Budding in YeastMolecular Biology of the Cell, 2003
- Attachment of the Ubiquitin-Related Protein Urm1p to the Antioxidant Protein Ahp1pEukaryotic Cell, 2003
- CSE1L/CAS: Its role in proliferation and apoptosisApoptosis, 2003
- Oxidants, oxidative stress and the biology of ageingNature, 2000
- A Protein Conjugation System in Yeast with Homology to Biosynthetic Enzyme Reaction of ProkaryotesJournal of Biological Chemistry, 2000
- Overexpression of recombinant proteins with a C‐terminal thiocarboxylate: Implications for protein semisynthesis and thiamin biosynthesisProtein Science, 1998
- Dislocation of Type I Membrane Proteins from the ER to the Cytosol Is Sensitive to Changes in Redox PotentialThe Journal of cell biology, 1998
- Export of Importin α from the Nucleus Is Mediated by a Specific Nuclear Transport FactorCell, 1997
- Antisense Inhibition of CAS, the Human Homologue of the Yeast Chromosome Segregation Gene CSE1, Interferes with Mitosis in HeLa CellsBiochemistry, 1997
- Interaction of tRNAs and of phosphorothioate-substituted nucleic acids with an organomercurial. Probing the chemical environment of thiolated residues by affinity electrophoresisBiochemistry, 1988