Bibliographic Details
| Title: |
Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense |
| Authors: |
Fanrui Kong, Zixuan Wang, Chuchu Zhang, Yihua Xiao, Muhammad Abdul Rehman Saeed, Weini Li, Akira Goto, Qingshuang Cai, Shanming Ji |
| Source: |
hLife, Vol 3, Iss 1, Pp 38-51 (2025) |
| Publisher Information: |
Elsevier, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
Cullin-3 (Cul3), death-associated inhibitor of apoptosis 2 (Diap2), death-related ced-3/Nedd2-like caspase (Dredd) ubiquitination, antimicrobial immune defense, Drosophila melanogaster, Medicine |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2949-9283 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2949928324000841; https://doaj.org/toc/2949-9283 |
| DOI: |
10.1016/j.hlife.2024.10.001 |
| Access URL: |
https://doaj.org/article/0aff5124589d467397f8f600e6824638 |
| Accession Number: |
edsdoj.0aff5124589d467397f8f600e6824638 |
| Database: |
Directory of Open Access Journals |
