热休克蛋白27通过隔离前半胱天冬酶-3和细胞色素c来抑制细胞色素c介导的半胱天冬酶激活。
Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c.
作者信息
Concannon C G, Orrenius S, Samali A
机构信息
Department of Biochemistry, National University of Ireland, Galway.
出版信息
Gene Expr. 2001;9(4-5):195-201. doi: 10.3727/000000001783992605.
Abstract
Mitochondrial cytochrome c release in response to pro-apoptotic signals leads to the formation of a cytochrome c/Apaf-1/procaspase-9 complex (the apoptosome) and resultant activation of caspase-9 and caspase-3. Here we demonstrate that the molecular chaperone, Hsp27, inhibits this cytochrome c-mediated activation of caspase-3. Immunodepeletion of Hsp27 from cytochrome c-activated cytosols resulted in decreased caspase activity. Furthermore, immunoprecipitation of Hsp27 resulted in the coprecipitation of both cytochrome c and procaspase-3. In reciprocal experiments, immunoprecipitation of both procaspase-3 and cytochrome c resulted in coprecipitation of Hsp27, indicating two independent interactions. These results point to Hsp27 mediating its inhibition of procaspase-3 activation through its ability to sequester both cytochrome c and procaspase-3, and thus prevent the correct formation/function of the apoptosome complex.
摘要
线粒体细胞色素c响应促凋亡信号而释放，导致细胞色素c/Apaf-1/前半胱天冬酶-9复合物（凋亡小体）的形成，并最终激活半胱天冬酶-9和半胱天冬酶-3。在此我们证明，分子伴侣Hsp27可抑制细胞色素c介导的半胱天冬酶-3激活。从细胞色素c激活的胞质溶胶中免疫去除Hsp27会导致半胱天冬酶活性降低。此外，Hsp27的免疫沉淀导致细胞色素c和前半胱天冬酶-3共沉淀。在反向实验中，前半胱天冬酶-3和细胞色素c的免疫沉淀导致Hsp27共沉淀，表明存在两种独立的相互作用。这些结果表明，Hsp27通过其隔离细胞色素c和前半胱天冬酶-3的能力介导其对前半胱天冬酶-3激活的抑制作用，从而阻止凋亡小体复合物的正确形成/功能。
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本文引用的文献
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Hsp27 protects mitochondria of thermotolerant cells against apoptotic stimuli.热休克蛋白27可保护耐热细胞的线粒体免受凋亡刺激。
Cell Stress Chaperones. 2001 Jan;6(1):49-58. doi: 10.1379/1466-1268(2001)006<0049:hpmotc>2.0.co;2.
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Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3.热休克蛋白27作为细胞色素c依赖性激活半胱天冬酶-3的负调控因子发挥作用。
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Heat shock proteins: regulators of stress response and apoptosis.热休克蛋白：应激反应和细胞凋亡的调节因子。
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