BH3-only Bcl-2 family members are coordinately regulated by the JNK pathway and require Bax to induce apoptosis in neurons.
BH3-only Bcl-2 family members are coordinately regulated by the JNK pathway and require Bax to induce apoptosis in neurons.
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DOI：
10.1074/jbc.m104073200
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发表时间：
2001-10
期刊：
影响因子：
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通讯作者：
Charles A. Harris;Eugene M. Johnson
中科院分区：
文献类型：
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作者：
Charles A. Harris;Eugene M. Johnson
Bcl-2蛋白家族是程序性细胞死亡的关键调控因子。仅bh3分子的一个独特亚家族已被确定，但其确切的作用机制尚不清楚。在这里，我们发现BH3-only Bcl-2家族成员，Dp5/Hrk和Bim，在Bax检查点上游被诱导神经元凋亡，其方式显示出对JNK信号的显著依赖。我们还发现Dp5和其他BH3-only蛋白以依赖bax的方式杀死小脑颗粒神经元。这些研究表明BH3-only成员的促凋亡活性不是独立的，而是需要多结构域的促凋亡Bcl-2家族成员的作用才能产生细胞死亡。
The Bcl-2 family of proteins are key regulators of programmed cell death. A distinct subfamily of BH3-only molecules has been identified, but their exact mechanism of action remains unclear. Here we show that the BH3-only Bcl-2 family members, Dp5/Hrk and Bim, are induced upstream of the Bax checkpoint in neuronal apoptosis in a manner that shows significant dependence on JNK signaling. We also show that Dp5 and other BH3-only proteins kill cerebellar granule neurons in a Bax-dependent manner. These studies demonstrate that BH3-only members do not act independently in their proapoptotic activities but rather require the action of multidomain proapoptotic Bcl-2 family members to produce cell death.