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Thevenon, D., Engel, E., Avet-Rochex, A., Gottar, M., Bergeret, E., Tricoire, H., Benaud, C., Baudier, J., Taillebourg, E., Fauvarque, M.O. (2009). The Drosophila ubiquitin-specific protease dUSP36/Scny targets IMD to prevent constitutive immune signaling.  Cell Host Microbe 6(4): 309--320.
FlyBase ID
FBrf0208983
Publication Type
Research paper
Abstract

Ubiquitin proteases remove ubiquitin monomers or polymers to modify the stability or activity of proteins and thereby serve as key regulators of signal transduction. Here, we describe the function of the Drosophila ubiquitin-specific protease 36 (dUSP36) in negative regulation of the immune deficiency (IMD) pathway controlled by the IMD protein. Overexpression of catalytically active dUSP36 ubiquitin protease suppresses fly immunity against Gram-negative pathogens. Conversely, silencing dUsp36 provokes IMD-dependent constitutive activation of IMD-downstream Jun kinase and NF-kappaB signaling pathways but not of the Toll pathway. This deregulation is lost in axenic flies, indicating that dUSP36 prevents constitutive immune signal activation by commensal bacteria. dUSP36 interacts with IMD and prevents K63-polyubiquitinated IMD accumulation while promoting IMD degradation in vivo. Blocking the proteasome in dUsp36-expressing S2 cells increases K48-polyubiquitinated IMD and prevents its degradation. Our findings identify dUSP36 as a repressor whose IMD deubiquitination activity prevents nonspecific activation of innate immune signaling.

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Related Publication(s)
Note

Tuning down NF-kappaB signaling by DUBs: a fly case.
Leulier, 2009, Cell Host Microbe 6(4): 294--296 [FBrf0208944]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Host Microbe
    Title
    Cell Host & Microbe
    Publication Year
    2007--
    ISBN/ISSN
    1931-3128 1934-6069
    Data From Reference
    Alleles (15)
    Gene Groups (1)
    Genes (11)
    Physical Interactions (4)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (1)
    Transgenic Constructs (12)