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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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | hLife |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949928324000841 |
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| author | Fanrui Kong Zixuan Wang Chuchu Zhang Yihua Xiao Muhammad Abdul Rehman Saeed Weini Li Akira Goto Qingshuang Cai Shanming Ji |
| author_facet | Fanrui Kong Zixuan Wang Chuchu Zhang Yihua Xiao Muhammad Abdul Rehman Saeed Weini Li Akira Goto Qingshuang Cai Shanming Ji |
| author_sort | Fanrui Kong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0aff5124589d467397f8f600e6824638 |
| institution | Kabale University |
| issn | 2949-9283 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | hLife |
| spelling | doaj-art-0aff5124589d467397f8f600e68246382025-01-23T05:28:06ZengElsevierhLife2949-92832025-01-01313851Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defenseFanrui Kong0Zixuan Wang1Chuchu Zhang2Yihua Xiao3Muhammad Abdul Rehman Saeed4Weini Li5Akira Goto6Qingshuang Cai7Shanming Ji8Center for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, ChinaCenter for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, ChinaCenter for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, ChinaCenter for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, ChinaCenter for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, ChinaDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope National Medical Center, California, USAINSERM, Université de Strasbourg, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), Bas-Rhin, FranceCenter for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, China; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Bas-Rhin, France; Correspondence:Center for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Anhui, China; Correspondence: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.http://www.sciencedirect.com/science/article/pii/S2949928324000841Cullin-3 (Cul3)death-associated inhibitor of apoptosis 2 (Diap2)death-related ced-3/Nedd2-like caspase (Dredd) ubiquitinationantimicrobial immune defenseDrosophila melanogaster |
| spellingShingle | Fanrui Kong Zixuan Wang Chuchu Zhang Yihua Xiao Muhammad Abdul Rehman Saeed Weini Li Akira Goto Qingshuang Cai Shanming Ji Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense hLife Cullin-3 (Cul3) death-associated inhibitor of apoptosis 2 (Diap2) death-related ced-3/Nedd2-like caspase (Dredd) ubiquitination antimicrobial immune defense Drosophila melanogaster |
| title | Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense |
| title_full | Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense |
| title_fullStr | Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense |
| title_full_unstemmed | Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense |
| title_short | Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense |
| title_sort | drosophila cul3 contributes to diap2 mediated innate immune signaling for antimicrobial defense |
| topic | Cullin-3 (Cul3) death-associated inhibitor of apoptosis 2 (Diap2) death-related ced-3/Nedd2-like caspase (Dredd) ubiquitination antimicrobial immune defense Drosophila melanogaster |
| url | http://www.sciencedirect.com/science/article/pii/S2949928324000841 |
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