The N-terminal fragment of gelsolin inhibits the interaction of DNase I with isolated actin, but not with the cofilin-actin complex
The N-terminal fragment of gelsolin inhibits the interaction of DNase I with isolated actin, but not with the cofilin-actin complex
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DOI：
10.1002/pmic.200401127
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发表时间：
2005-08-01
期刊：
影响因子：
3.4
通讯作者：
dos Remedios, CG
中科院分区：
文献类型：
--
作者：
Chhabra, D;Nosworthy, NJ;dos Remedios, CG
细胞凋亡在胚胎发育、免疫系统细胞的克隆选择和癌症预防中至关重要。凋亡细胞在形态学上显示出特征性变化，这些变化先于最终导致细胞死亡的核DNA片段化。目前的证据表明，DNA酶I负责细胞凋亡过程中的DNA水解。在体内，很可能细胞质肌动蛋白结合并抑制DNA酶I的酶活性和核转位，并且肌动蛋白-DNA酶I复合物的破坏导致DNA酶I的活化。在这份报告中，我们证明了凝溶胶蛋白（N-凝溶胶蛋白）的N-末端片段破坏肌动蛋白-DNA酶I的相互作用。这为N-凝溶胶蛋白在调节DNA酶I活性中的作用提供了分子机制。我们还表明，cofilin通过形成三元复合物，防止N-凝溶胶蛋白从肌动蛋白释放DNA酶I，从而稳定肌动蛋白-DNA酶I复合物。我们认为，cofilin和凝溶胶蛋白是必不可少的调节从肌动蛋白的DNA酶I的释放。
Apoptosis is essential in embryonic development, clonal selection of cells of the immune system and in the prevention of cancer. Apoptotic cells display characteristic changes in morphology that precede the eventual fragmentation of nuclear DNA resulting in cell death. Current evidence implicates DNase I as responsible for hydrolysis of DNA during apoptosis. In vivo, it is likely that cytoplasmic actin binds and inhibits the enzymatic activity and nuclear translocation of DNase I and that disruption of the actin-DNase I complex results in activation of DNase I. In this report we demonstrate that the N-terminal fragment of gelsolin (N-gelsolin) disrupts the actin-DNase I interaction. This provides a molecular mechanism for the role of the N-gelsolin in regulating DNase I activity. We also show that cofilin stabilises the actin-DNase I complex by forming a ternary complex that prevents N-gelsolin from releasing DNase I from actin. We suggest that both cofilin and gelsolin are essential in modulating the release of DNase I from actin.