A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells.
A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells.
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DOI：
10.1038/onc.2009.118
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发表时间：
2009-07-16
期刊：
影响因子：
8
通讯作者：
Saikumar, P.
中科院分区：
文献类型：
--
作者：
Kar, R.;Singha, P. K.;Venkatachalam, M. A.;Saikumar, P.
硫醇反应性环戊烯酮前列腺素，15-脱氧-Δ12，14-前列腺素J2，在结肠癌、乳腺癌和前列腺癌细胞系中诱导了一种新的非凋亡和Map 1 LC 3依赖性但非自噬形式的细胞死亡，其特征在于广泛的细胞质空泡化伴内质网扩张。巯基稳态的破坏，导致ER应激，泛素化蛋白的积累和随后的ER扩张，导致15 d-PGJ 2的PPARγ非依赖性细胞死亡。电子显微镜显示这些空泡中细胞内细胞器的缺失和核纤层蛋白B的独特断裂，表明这种形式的细胞死亡不同于自噬和凋亡。放线菌酮和放线菌素D阻止了15 d-PGJ 2诱导的细胞死亡，表明细胞质空泡化死亡需要新的蛋白质合成。在这里，我们首次报道了自噬标志物LC 3的上调和处理是非自噬性细胞质空泡化和细胞死亡中的重要事件。值得注意的是，LC 3的敲低赋予了针对15 d-PGJ 2诱导的细胞质空泡化和细胞死亡的显著保护，这表明LC 3在除自噬之外的死亡过程中的新作用。
Thiol reactive cyclopentenone prostaglandin, 15-deoxy-Δ12, 14-Prostaglandin J2, induced a novel, non-apoptotic and Map1 LC3 dependent but non-autophagic form of cell death in colon, breast and prostate cancer cell lines, characterized by extensive cytoplasmic vacuolation with dilatation of endoplasmic reticulum. Disruption of sulfhydryl homeostasis, which resulted in ER stress, accumulation of ubiquitinated proteins and subsequent ER dilation, contributed to PPARγ independent cell death by 15d-PGJ2. Absence of intracellular organelles in these vacuoles, shown by Electron Microscopy and unique fragmentation of Lamin B, suggested this form of cell death to be different from autophagy and apoptosis. Cell death induced by 15d-PGJ2 is prevented by cycloheximide and actinomycin D, suggesting a requirement of new protein synthesis for death with cytoplasmic vacuolation. Here, we report for the first time that upregulation and processing of autophagy marker LC3 is an important event in non-autophagic cytoplasmic vacuolation and cell death. Notably, knockdown of LC3 conferred significant protection against 15d-PGJ2 induced cytoplasmic vacuolation and cell death suggesting a novel role of LC3 in a death process other than autophagy.
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DOI：
10.1152/ajpendo.00274.2006
发表时间：
2007-04-01
影响因子：
5.1
作者：
Chambers, Kari T.;Weber, Sarah M.;Corbett, John A.
通讯作者：
Corbett, John A.
影响因子：
2.9
作者：
Ishii, T;Sakurai, T;Uchida, K
通讯作者：
Uchida, K
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
2.3
作者：
Chen, SY;Lu, FJ;Huang, TS
通讯作者：
Huang, TS
影响因子：
6.1
作者：
Kimura, Hideki;Li, Xuan;Yoshida, Haruyoshi
通讯作者：
Yoshida, Haruyoshi