Cellular and Molecular Life Sciences

, Volume 73, Issue 9, pp 1939–1954 | Cite as

Urm1: an essential regulator of JNK signaling and oxidative stress in Drosophila melanogaster

Original Article

Abstract

Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL) with the dual capacity to act both as a sulphur carrier and posttranslational protein modifier. Here we characterize the Drosophila melanogaster homologues of Urm1 (CG33276) and its E1 activating enzyme Uba4 (CG13090), and show that they function together to induce protein urmylation in vivo. Urm1 conjugation to target proteins in general, and to the evolutionary conserved substrate Peroxiredoxin 5 (Prx5) specifically, is dependent on Uba4. A complete loss of Urm1 is lethal in flies, although a small number of adult zygotic Urm1n123 mutant escapers can be recovered. These escapers display a decreased general fitness and shortened lifespan, but in contrast to their S. cerevisiae counterparts, they are resistant to oxidative stress. Providing a molecular explanation, we demonstrate that cytoprotective JNK signaling is increased in Urm1 deficient animals. In agreement, molecular and genetic evidence suggest that elevated activity of the JNK downstream target genes Jafrac1 and gstD1 strongly contributes to the tolerance against oxidative stress displayed by Urm1n123 null mutants. In conclusion, Urm1 is a UBL that is involved in the regulation of JNK signaling and the response against oxidative stress in the fruit fly.

Keywords

Urm1 Drosophila Oxidative stress UBL JNK pathway 

Notes

Acknowledgments

We would like to thank members of the scientific community who generously shared reagents critical to this work. In addition, we thank Ruth H. Palmer, Mattias Alenius and Yasuo Yamazaki for critical reading of the manuscript and for scientific discussions. We also acknowledge the Drosophila Genomics Resource Center (DGRC), supported by NIH grant 2P40OD010949-10A1, for providing cDNA clones and vectors and the Bloomington Drosophila Stock Center (NIH P40OD018537) for fly stocks. This work was supported by the Swedish Foundation for Strategic research (SSF), The Swedish Research Council, Jeanssons Stiftelser and Insamlingsstiftelsen för medicinsk forskning vid Umeå Universitet.

Supplementary material

18_2015_2121_MOESM1_ESM.pdf (847 kb)
Supplementary material 1 (PDF 847 kb)

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© Springer International Publishing 2015

Authors and Affiliations

  1. 1.Department of Molecular BiologyUmeå UniversityUmeåSweden

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