HSpin1, a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase-independent autophagic cell death
HSpin1, a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase-independent autophagic cell death
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DOI：
10.1038/sj.cdd.4401246
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发表时间：
2003-07
影响因子：
12.4
通讯作者：
H. Yanagisawa;T. Miyashita;Y. Nakano;Daisuke Yamamoto
中科院分区：
文献类型：
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作者：
H. Yanagisawa;T. Miyashita;Y. Nakano;Daisuke Yamamoto
果蝇Spinter(Spin)基因产物是神经系统和生殖系统中细胞程序性死亡所必需的。我们已经确定了果蝇Spin基因产物(HSpin1)的人类同源物。在肿瘤坏死因子-α处理的细胞中，HSpin1与Bcl2和凋亡调节剂Bclx(Bclx L)结合，但不与Bcl2相关X蛋白和Bcl2同源拮抗剂KIL1等促凋亡成员结合。外源表达HSpin1导致细胞死亡，但不诱导细胞色素c从线粒体释放。过表达Bclx可抑制HSpin1诱导的细胞死亡。有趣的是，一种坏死抑制剂，吡咯烷二硫代氨基甲酸酯，而不是pancaspase抑制剂，碳苯氧基-VAD-氟甲基酮和p35，阻止了HSpin1诱导的细胞死亡。HSpin1诱导的细胞死亡增加了自噬空泡和成熟形式的组织蛋白酶D，提示了一种新的caspase非依赖的细胞死亡，这与自噬有关。
The Drosophila spinster (spin) gene product is required for programmed cell death in the nervous and reproductive systems. We have identified a human homologue of the Drosophila spin gene product (HSpin1). HSpin1 bound to Bcl-2 and apoptosis regulator Bcl-X (Bcl-x L), but not to proapoptotic members such as Bcl-2-associated X protein and Bcl-2 homologous antagonist killer, in cells treated with TNF-α. Exogenous expression of HSpin1 resulted in the cell death without inducing a release of cytochrome c from mitochondria. Overexpression of Bcl-x L inhibited the HSpin1-induced cell death. Interestingly, a necrosis inhibitor, pyrrolidine dithiocarbomate, but not the pancaspase inhibitors, carbobenzoxy-VAD-fluoromethyl ketone and p35, blocked the HSpin1-induced cell death. HSpin1-induced cell death increases autophagic vacuole and mature form of cathepsin D, suggesting a novel caspase-independent cell death, which is link to autophagy.