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 constitu...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.Weshow 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.展开更多
A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combinati...A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combination of NMR,ECD spectroscopy,and X-ray difraction analysis.Compounds 1 and 6-8 were tested to exhibit potential antitumor properties,of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest.In addition,these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines,as well as suppress lung cancer A549 cells metastasis in vitro.展开更多
文摘去泛素化酶（deubiquitinating enzymes， DUBs）能对抗泛素连接酶（ubiquitin ligases），从而调节靶信号分子的泛素化和稳定性。在果蝇体内，泛素-蛋白酶体系统在调节凋亡方面发挥关键作用，最明显的是通过控制主要的凋亡调节因子--果蝇凋亡抑制蛋白1（Drosophila inhibitor of apoptosis protein 1， DIAP1）的丰度来调节凋亡。虽然基于DIAP1的泛素化机制已被广泛研究，但是DUBs在控制DIAP1活性中的确切作用仍未得到充分研究。
基金supported by grants from the National Natural Science Foundation of China(32100702).
文摘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.Weshow 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.
基金supported by the NSFC-Joint Foundation of Yunnan Province(U1902213)Chongqing Municipal Natural Science Foundation(cstc2018jcyjAX0388)+3 种基金the Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK0502)Southeast Asia Biodiversity Research Institute,CAS(2017CASSEABRIQG003)State Key Laboratory of Phytochemistry and Plant Resources in West China(P2017-KF02 and P2019-ZZ05)the Natural Sciences Foundation of Yunnan Province(2019FA003).
文摘A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combination of NMR,ECD spectroscopy,and X-ray difraction analysis.Compounds 1 and 6-8 were tested to exhibit potential antitumor properties,of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest.In addition,these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines,as well as suppress lung cancer A549 cells metastasis in vitro.
