Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense
The host antimicrobial immune response relies on a complex interplay of molecular mechanisms to effectively combat microbial infections. Herein, we investigate the functional role of Cullin-3 (Cul3), one critical constituent of Cullin-RING ubiquitin ligases, in the Drosophila melanogaster (fruit fly...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
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| Series: | hLife |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949928324000841 |
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| Summary: | The host antimicrobial immune response relies on a complex interplay of molecular mechanisms to effectively combat microbial infections. Herein, we investigate the functional role of Cullin-3 (Cul3), one critical constituent of Cullin-RING ubiquitin ligases, in the Drosophila melanogaster (fruit fly) antimicrobial immune defense. We show that silencing of Cul3 leads to a decreased induction of antimicrobial peptides and high mortality in adult flies after bacterial infection. Through biochemical approaches, we demonstrate that Cul3 predominantly relies on its BTB-binding domain and neddylation domain to physically associate with death-associated inhibitor of apoptosis 2 (Diap2). Importantly, Cul3 ameliorates the Diap2-mediated ubiquitination of death-related ced-3/Nedd2-like caspase (Dredd), a process essential for robust immune deficiency signaling upon bacterial infection. Taken together, our findings highlight a previously unrecognized regulatory axis of Cul3/Diap2/Dredd in the fly antimicrobial immune defense, providing potential insights into therapeutic strategies for combating bacterial infections in humans. |
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| ISSN: | 2949-9283 |