Inhibition of apoptosis by the actin-regulatory protein gelsolin
Inhibition of apoptosis by the actin-regulatory protein gelsolin
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DOI：
10.1093/emboj/16.15.4650
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发表时间：
1997-08-01
期刊：
影响因子：
11.4
通讯作者：
Kuzumaki, N
中科院分区：
文献类型：
--
作者：
Ohtsu, M;Sakai, N;Kuzumaki, N
Gelsolin是一种肌动蛋白调节蛋白，可调节肌动蛋白的组装和拆卸，并被认为通过调节肌动蛋白网络来调节体内细胞运动。除了具有肌动蛋白调节功能外，gelsolin也被提出影响细胞生长，我们目前的实验已经测试了gelsolin可能参与细胞凋亡的调节，细胞凋亡受生长的显著影响，当gelsolin在Jurkat细胞中过表达时，gelsolin强烈抑制抗Fas抗体、c -2神经酰胺或地塞米松诱导的细胞凋亡，而不改变F-actin的形态或Fas或Bcl-2家族蛋白的水平。在诱导凋亡后，在对照载体转染物中观察到CPP32（like）蛋白酶活性增加，而在gelsolin转染物中则被强烈抑制，在gelsolin转染物中抗fas处理后，CPP32蛋白酶的失活形式Pro-CPP32蛋白保持不裂解，表明gelsolin阻断了该蛋白酶的上游，CPP32（like）蛋白酶的四肽抑制剂强烈抑制fas介导的凋亡。但仅部分抑制c -2神经酰胺和地塞米松诱导的细胞凋亡，这些数据表明，在Jurkat细胞中，负责执行凋亡的关键靶点可能存在于CPP32（样）蛋白酶的上游，凝胶胶作用于该靶点抑制凋亡细胞死亡程序。
Gelsolin is an actin-regulatory protein that modulates actin assembly and disassembly, and is believed to regulate cell motility in vivo through modulation of the actin network. In addition to its actin-regulatory function, gelsolin has also been proposed to affect cell growth, Our present experiments have tested the possible involvement of gelsolin in the regulation of apoptosis, which is significantly affected by growth, When overexpressed in Jurkat cells, gelsolin strongly inhibited apoptosis induced by anti-Fas antibody, C-2-ceramide or dexamethasone, without changing the F-actin morphology or the levels of Fas or Bcl-2 family proteins, Upon the induction of apoptosis, an increase in CPP32(-like) protease activity was observed in the control vector transfectants, while it was strongly suppressed in the gelsolin transfectants, Pro-CPP32 protein, an inactive form of CPP32 protease, remained uncleaved by anti-Fas treatment in the gelsolin transfectants, indicating that gelsolin blocks upstream of this protease, The tetrapeptide inhibitor of CPP32(-like) proteases strongly inhibited Fas-mediated apoptosis, but only partially suppressed both C-2-ceramide- and dexamethasone-induced apoptosis, These data suggest that the critical target responsible for the execution of apoptosis may exist upstream of CPP32(-like) proteases in Jurkat cells and that gelsolin acts on this target to inhibit the apoptotic cell death program.