Innate immune signaling in Drosophila is regulated by transforming growth factor ß (TGFß)-activated kinase (Tak1)-triggered ubiquitin editing.
J Biol Chem
; 292(21): 8738-8749, 2017 05 26.
Article
em En
| MEDLINE
| ID: mdl-28377500
ABSTRACT
Coordinated regulation of innate immune responses is necessary in all metazoans. In Drosophila the Imd pathway detects Gram-negative bacterial infections through recognition of diaminopimelic acid (DAP)-type peptidoglycan and activation of the NF-κB precursor Relish, which drives robust antimicrobial peptide gene expression. Imd is a receptor-proximal adaptor protein homologous to mammalian RIP1 that is regulated by proteolytic cleavage and Lys-63-polyubiquitination. However, the precise events and molecular mechanisms that control the post-translational modification of Imd remain unclear. Here, we demonstrate that Imd is rapidly Lys-63-polyubiquitinated at lysine residues 137 and 153 by the sequential action of two E2 enzymes, Ubc5 and Ubc13-Uev1a, in conjunction with the E3 ligase Diap2. Lys-63-ubiquitination activates the TGFß-activated kinase (Tak1), which feeds back to phosphorylate Imd, triggering the removal of Lys-63 chains and the addition of Lys-48 polyubiquitin. This ubiquitin-editing process results in the proteasomal degradation of Imd, which we propose functions to restore homeostasis to the Drosophila immune response.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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MAP Quinase Quinase Quinases
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Proteínas de Drosophila
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Ubiquitinação
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Imunidade Inata
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article