C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death.
C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death.
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基于线虫的筛选鉴定出可诱导 STAT3 依赖性溶酶体细胞死亡的溶酶体损伤生物碱
DOI：
10.1007/s13238-018-0520-0
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发表时间：
2018-12
期刊：
影响因子：
21.1
通讯作者：
Yang C
中科院分区：
文献类型：
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作者：
Li Y;Zhang Y;Gan Q;Xu M;Ding X;Tang G;Liang J;Liu K;Liu X;Wang X;Guo L;Gao Z;Hao X;Yang C
溶酶体是细胞内的降解和信号传导中心，它们的功能障碍损害了多种细胞过程。为了了解溶酶体损伤的细胞效应，我们以秀丽隐杆线虫（C. elegans）为模型系统筛选了诱导溶酶体异常的天然小分子化合物。在线虫巨噬细胞样细胞中鉴定出一组沃巴辛基-伊博根型双吲哚生物碱（ervachinines A - d）引起溶酶体增大。有趣的是，这些化合物在独立于典型凋亡途径的生殖系中触发细胞死亡。在哺乳动物细胞中，ervachinine A-D诱导溶酶体增大和损伤，导致组织蛋白酶蛋白酶渗漏，抑制自噬体降解和坏死细胞死亡。进一步分析发现，这种ervachine诱导的溶酶体损伤和溶酶体细胞死亡依赖于STAT3信号，而不依赖于RIP1或RIP3信号。这些发现表明，溶酶体损伤化合物是分析溶酶体稳态和溶酶体相关人类疾病的信号机制的有希望的试剂。
Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A–D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A–D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.
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影响因子：
5.3
作者：
Ono, K;Kim, SO;Han, JH
通讯作者：
Han, JH
早期到晚期内体转化中磷脂酰肌醇 3-磷酸水平的负调节
DOI：
10.1083/jcb.201506081
发表时间：
2016-01-18
期刊：
The Journal of cell biology
影响因子：
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作者：
Liu K;Jian Y;Sun X;Yang C;Gao Z;Zhang Z;Liu X;Li Y;Xu J;Jing Y;Mitani S;He S;Yang C
通讯作者：
Yang C
影响因子：
64.8
作者：
Perera, RushikaM.;Stoykova, Svetlana;Nicolay, Brandon N.;Ross, Kenneth N.;Fitamant, Julien;Boukhali, Myriam;Lengrand, Justine;Deshpande, Vikram;Selig, Martin K.;Ferrone, Cristina R.;Settleman, Jeff;Stephanopoulos, Gregory;Dyson, Nicholas J.;Zoncu, Roberto;Ramaswamy, Sridhar;Haas, Wilhelm;Bardeesy, Nabeel
通讯作者：
Bardeesy, Nabeel
影响因子：
2.9
作者：
Almaguel, Frankis G.;Liu, Jo-Wen;Pacheco, Fabio J.;De Leon, Daisy;Casiano, Carlos A.;De Leon, Marino
通讯作者：
De Leon, Marino
影响因子：
21.3
作者：
通讯作者：
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