ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death.
ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death.
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作者：
Zhaorigetu S;Wan G;Kaini R;Jiang Z;Hu CA
我们最近报道了一种新的仅含BH 3的促死亡蛋白载脂蛋白L1（ApoL 1）的鉴定和表征，当其过表达时，可诱导多种细胞（包括来自正常和癌组织的细胞）中的自噬性细胞死亡（ACD）。ApoL 1未能在自噬缺陷的Atg 5 −/−和Atg 7 −/− MEF细胞中诱导ACD，这表明ApoL 1诱导的细胞死亡确实是自噬依赖的。此外，ApoL 1的BH 3结构域缺失等位基因不能诱导ACD，表明ApoL 1是真正的仅BH 3促死亡蛋白。为了进一步研究ApoL 1表达的调控，我们发现ApoL 1在人脐静脉内皮细胞中可被干扰素-γ和肿瘤坏死因子-α诱导，这表明ApoL 1可能在精氨酸诱导的炎症反应中发挥作用。此外，我们观察到，ApoL 1是一种脂质结合蛋白，对磷脂酸和心磷脂具有高亲和力，而对各种磷酸肌醇的亲和力较低。功能基因组学分析在人类ApoL 1结构基因的编码外显子中鉴定出5种非同义单核苷酸多态性（NSNPs）-所有5种NSNPs都可能导致ApoL 1活性的有害改变。最后，我们讨论了ApoL 1与各种人类疾病之间的联系。
We recently reported the identification and characterization of a novel BH3-only pro-death protein, apolipoprotein L1 (ApoL1), that, when overexpressed, induces autophagic cell death (ACD) in a variety of cells, including those originated from normal and cancerous tissues. ApoL1 failed to induce ACD in autophagy-deficient Atg5−/− and Atg7−/− MEF cells, suggesting that ApoL1-induced cell death is indeed autophagy-dependent. In addition, a BH3 domain deletion allele of ApoL1 was unable to induce ACD, demonstrating that ApoL1 is a bona fide BH3-only pro-death protein. To further investigate regulation of ApoL1 expression, we showed that ApoL1 is inducible by interferon-γ and tumor necrosis factor-α in human umbilical vein endothelial cells, suggesting that ApoL1 may play a role in cytokine-induced inflammatory response. Moreover, we observed that ApoL1 is a lipid-binding protein with high affinity for phosphatidic acid and cardiolipin and less affinity for various phosphoinositides. Functional genomics analysis identified 5 nonsynonymous single nucleotide polymorphisms (NSNPs) in the coding exons of the human ApoL1 structural gene– all the 5 NSNPs may cause deleterious alteration of ApoL1 activity. Finally, we discuss the link between ApoL1 and various human diseases.
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DOI：
10.1084/jem.20071463
发表时间：
2008-08-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Molina-Portela MP;Samanovic M;Raper J
通讯作者：
Raper J
影响因子：
4.8
作者：
Petiot, A;Ogier-Denis, E;Codogno, P
通讯作者：
Codogno, P
影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
DOI：
10.1073/pnas.032069099
发表时间：
2002-04-02
影响因子：
11.1
作者：
Mimmack, ML;Ryan, M;Bahn, S
通讯作者：
Bahn, S
影响因子：
4.8
作者：
Hekman, Mirko;Albert, Stefan;Rapp, Ulf R.
通讯作者：
Rapp, Ulf R.