Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18
Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18
复制标题
Bcl-XL/Bcl-2 靶向化合物 Z18 诱导不依赖 Beclin 1 的自噬
DOI：
10.4161/auto.6.8.13336
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发表时间：
2010-11-16
期刊：
影响因子：
13.3
通讯作者：
Xia, Bin
中科院分区：
文献类型：
--
作者：
Tian, Songhai;Lin, Jian;Xia, Bin
Bcl-XL/Bcl-2的抑制剂可以通过从其与这些蛋白质的复合物中释放自噬蛋白Beclin 1来诱导自噬。在这里，我们报告了一种靶向Bcl-XL/Bcl-2的BH 3结合沟的新型化合物，Z18，其有效地诱导HeLa细胞中自噬相关的细胞死亡，而没有明显的凋亡。出乎意料的是，Beclin 1和磷脂酰肌醇3-激酶的抑制对Z18诱导的HeLa细胞自噬没有明显的影响，这意味着它是一种非典型的Beclin 1非依赖性自噬。同时，自噬体的积累与Z18诱导的细胞死亡正相关，自噬的全流量不是必需的。
Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.