Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1
Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1
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DOI：
10.1016/j.molcel.2006.12.013
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发表时间：
2007-01-26
期刊：
影响因子：
16
通讯作者：
Shi, Yigong
中科院分区：
文献类型：
--
作者：
Bao, Qing;Lu, Wenyun;Shi, Yigong
Apaf-1 在细胞凋亡中发挥重要作用。在细胞色素 c 和 dATP 存在的情况下，Apaf-1 组装成寡聚凋亡体，负责激活 procaspase-9 并维持加工后的 caspase-9 的酶活性。其他细胞因子对凋亡体组装的调节知之甚少。在这里，我们报道了钙离子的生理浓度通过抑制单体、自抑制 Apaf-1 蛋白中的核苷酸交换对凋亡体的组装产生负面影响。因此，钙会阻断 Apaf-1 激活 caspase-9 的能力。这些观察结果表明钙稳态对 Apaf-1 依赖性细胞凋亡途径具有重要作用。
Apaf-1 plays an essential role in apoptosis. In the presence of cytochrome c and dATP, Apaf-1 assembles into an oligomeric apoptosome, which is responsible for the activation of procaspase-9 and the maintenance of the enzymatic activity of the processed caspase-9. Regulation of apoptosome assembly by other cellular factors is poorly understood. Here we report that physiological concentrations of calcium ion negatively affect the assembly of apoptosome by inhibiting nucleotide exchange in the monomeric, autoinhibited Apaf-1 protein. Consequently, calcium blocks the ability of Apaf-1 to activate caspase-9. These observations suggest an important role of calcium homeostasis on the Apaf-1-dependent apoptotic pathway.