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Citation
Anjum, S.G., Xu, W., Nikkholgh, N., Basu, S., Nie, Y., Thomas, M., Satyamurti, M., Budnik, B.A., Ip, Y.T., Veraksa, A. (2013). Regulation of Toll Signaling and Inflammation by β-Arrestin and the SUMO Protease Ulp1.  Genetics 195(4): 1307--1317.
FlyBase ID
FBrf0223495
Publication Type
Research paper
Abstract

The Toll signaling pathway has a highly conserved function in innate immunity and is regulated by multiple factors that fine tune its activity. One such factor is β-arrestin Kurtz (Krz), which we previously implicated in the inhibition of developmental Toll signaling in the Drosophila melanogaster embryo. Another level of controlling Toll activity and immune system homeostasis is by protein sumoylation. In this study, we have uncovered a link between these two modes of regulation and show that Krz affects sumoylation via a conserved protein interaction with a SUMO protease, Ulp1. Loss of function of krz or Ulp1 in Drosophila larvae results in a similar inflammatory phenotype, which is manifested as increased lamellocyte production; melanotic mass formation; nuclear accumulation of Toll pathway transcriptional effectors, Dorsal and Dif; and expression of immunity genes, such as Drosomycin. Moreover, mutations in krz and Ulp1 show dosage-sensitive synergistic genetic interactions, suggesting that these two proteins are involved in the same pathway. Using Dorsal sumoylation as a readout, we found that altering Krz levels can affect the efficiency of SUMO deconjugation mediated by Ulp1. Our results demonstrate that β-arrestin controls Toll signaling and systemic inflammation at the level of sumoylation.

PubMed ID
PubMed Central ID
PMC3832275 (PMC) (EuropePMC)
Related Publication(s)
Teaching note

A Roadmap to Understanding Toll Pathway Changes: An Educational Primer for Use with "Regulation of Toll Signaling and Inflammation by β-Arrestin and the SUMO Protease Ulp1".
Schmidt, 2014, Genetics 196(4): 923--929 [FBrf0224652]

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genetics
    Title
    Genetics
    Publication Year
    1916-
    ISBN/ISSN
    0016-6731
    Data From Reference
    Alleles (10)
    Gene Groups (1)
    Genes (8)
    Physical Interactions (5)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (2)
    Transgenic Constructs (7)