| RRC ID |
59176
|
| 著者 |
Cammarata-Mouchtouris A, Nguyen XH, Acker A, Bonnay F, Goto A, Orian A, Fauvarque MO, Boutros M, Reichhart JM, Matt N.
|
| タイトル |
Hyd ubiquitinates the NF-κB co-factor Akirin to operate an effective immune response in Drosophila.
|
| ジャーナル |
PLoS Pathog
|
| Abstract |
The Immune Deficiency (IMD) pathway in Drosophila melanogaster is activated upon microbial challenge with Gram-negative bacteria to trigger the innate immune response. In order to decipher this nuclear factor κB (NF-κB) signaling pathway, we undertook an in vitro RNAi screen targeting E3 ubiquitin ligases specifically and identified the HECT-type E3 ubiquitin ligase Hyperplastic discs (Hyd) as a new actor in the IMD pathway. Hyd mediated Lys63 (K63)-linked polyubiquitination of the NF-κB cofactor Akirin was required for efficient binding of Akirin to the NF-κB transcription factor Relish. We showed that this Hyd-dependent interaction was required for the transcription of immunity-related genes that are activated by both Relish and Akirin but was dispensable for the transcription of genes that depend solely on Relish. Therefore Hyd is key in NF-κB transcriptional selectivity downstream of the IMD pathway. Drosophila depleted of Akirin or Hyd failed to express the full set of genes encoding immune-induced anti-microbial peptides and succumbed to immune challenges. We showed further that UBR5, the mammalian homolog of Hyd, was also required downstream of the NF-κB pathway for the activation of Interleukin 6 (IL6) transcription by LPS or IL-1β in cultured human cells. Our findings link the action of an E3 ubiquitin ligase to the activation of immune effector genes, deepening our understanding of the involvement of ubiquitination in inflammation and identifying a potential target for the control of inflammatory diseases.
|
| 巻・号 |
16(4)
|
| ページ |
e1008458
|
| 公開日 |
2020-4-1
|
| DOI |
10.1371/journal.ppat.1008458
|
| PII |
PPATHOGENS-D-19-00815
|
| PMID |
32339205
|
| PMC |
PMC7205318
|
| MeSH |
Animals
Drosophila
Drosophila Proteins / genetics
Drosophila Proteins / immunology*
Drosophila melanogaster / genetics
Drosophila melanogaster / immunology*
Drosophila melanogaster / microbiology
Gram-Negative Bacteria / physiology
HeLa Cells
Humans
Immunity, Innate
Nuclear Proteins / genetics
Nuclear Proteins / immunology*
Transcription Factors / genetics
Transcription Factors / immunology*
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / immunology*
Ubiquitination
|
| IF |
6.218
|
| 引用数 |
0
|
| リソース情報 |
| ショウジョウバエ |
|
