Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis
Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis
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DOI：
10.1038/sj.cdd.4400840
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发表时间：
2001-05-01
影响因子：
12.4
通讯作者：
Cryns, VL
中科院分区：
文献类型：
--
作者：
Byun, Y;Chen, F;Cryns, VL
半胱天冬酶是细胞凋亡的关键介质。我们利用一种新的表达克隆策略来鉴定编码半胱天冬酶底物的cDNA，分离出作为半胱天冬酶底物的中间丝蛋白波形蛋白，波形蛋白在体外被多个半胱天冬酶在不同位点优先切割，包括天冬氨酸（85）被半胱天冬酶-3和-7切割，天冬氨酸（259）被半胱天冬酶-6切割，产生多个蛋白水解片段。在多种刺激诱导的细胞凋亡过程中，波形蛋白被多个半胱天冬酶迅速水解成大小相似的片段。波形蛋白的半胱天冬酶裂解破坏其中间丝的细胞质网络，并与核碎裂时间一致。此外，波形蛋白在Asp（85）处的半胱天冬酶蛋白水解产生促凋亡氨基末端片段，其诱导凋亡的能力依赖于半胱天冬酶。总之，我们的发现表明波形蛋白的半胱天冬酶蛋白水解通过拆除中间丝和通过促凋亡切割产物放大细胞死亡信号来促进凋亡。
Caspases are key mediators of apoptosis, Using a novel expression cloning strategy we recently developed to identify cDNAs encoding caspase substrates, we isolated the intermediate filament protein vimentin as a caspase substrate, vimentin is preferentially cleaved by multiple caspases at distinct sites in vitro, including Asp(85) by caspases-3 and -7 and Asp(259) by caspase-6, to yield multiple proteolytic fragments. Vimentin is rapidly proteolyzed by multiple caspases into similar sized fragments during apoptosis induced by many stimuli. Caspase cleavage of vimentin disrupts its cytoplasmic network of intermediate filaments and coincides temporally with nuclear fragmentation. Moreover, caspase proteolysis of vimentin at Asp(85) generates a pro apoptotic amino-terminal fragment whose ability to induce apoptosis is dependent on caspases, Taken together, our findings suggest that caspase proteolysis of vimentin promotes apoptosis by dismantling intermediate filaments and by amplifying the cell death signal via a pro-apoptotic cleavage product.