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PMID:19837371

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Citation

Thevenon, D, Engel, E, Avet-Rochex, A, Gottar, M, Bergeret, E, Tricoire, H, Benaud, C, Baudier, J, Taillebourg, E and Fauvarque, MO (2009) The Drosophila ubiquitin-specific protease dUSP36/Scny targets IMD to prevent constitutive immune signaling. Cell Host Microbe 6:309-20

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.

Links

PubMed Online version:10.1016/j.chom.2009.09.007

Keywords

Animals; Drosophila/immunology; Drosophila Proteins/physiology; Endopeptidases/physiology; Gene Dosage; Gene Expression Regulation; Gene Silencing; Germ-Free Life/immunology; Gram-Negative Bacteria/immunology; JNK Mitogen-Activated Protein Kinases/biosynthesis; NF-kappa B/biosynthesis; Protein Interaction Mapping; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:UBP36

involved_in

GO:0061060: negative regulation of peptidoglycan recognition protein signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBP36

enables

GO:0061578: Lys63-specific deubiquitinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:UBP36

involved_in

GO:0070536: protein K63-linked deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBP36

involved_in

GO:1901800: positive regulation of proteasomal protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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