Small stress proteins as novel regulators of apoptosis - Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death
Small stress proteins as novel regulators of apoptosis - Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death
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DOI：
10.1074/jbc.271.28.16510
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发表时间：
1996-07-12
影响因子：
4.8
通讯作者：
Arrigo, AP
中科院分区：
文献类型：
--
作者：
Mehlen, P;SchulzeOsthoff, K;Arrigo, AP
小应激蛋白的表达提高了暴露于大量损伤诱导坏死细胞死亡的哺乳动物细胞的存活率。细胞表面受体Fas/APO-1及其配体是细胞凋亡的重要介质。本研究表明，人热休克蛋白（hsp）27在小鼠L929细胞中的组成性表达可阻断Fas/ apo -1介导的细胞死亡。人hsp27的表达可阻止抗apo -1诱导的DNA断裂和形态变化。这些结果强烈提示人hsp27可作为Fas/ apo -1诱导的细胞凋亡抑制剂。我们还报道了来自不同物种的小应激蛋白的表达，如人hsp27、果蝇Dhsp27或人α b -晶体蛋白，赋予对staurosporine（一种蛋白激酶C抑制剂）诱导的凋亡细胞死亡的抗性。因此，小应激蛋白是一种新的调控因子，能够阻断不同途径诱导的细胞凋亡。
Small stress protein expression enhances the survival of mammalian cells exposed to numerous injuries that induce necrotic cell death. The cell surface receptor Fas/APO-1 and its ligand have been recently identified as important mediators of apoptosis. Here, we show that constitutive expression of human heat shock protein (hsp)27 in murine L929 cells blocks Fas/APO-1-mediated cell death. Expression of human hsp27 prevented anti-APO-1-induced DNA fragmentation and morphological changes. These results strongly suggest that human hsp27 acts as a cellular inhibitor of Fas/APO-1-induced apoptosis. We also report that the expression of small stress proteins from different species, such as human hsp27, Drosophila Dhsp27, or human alpha B-crystallin, confers resistance to apoptotic cell death induced by staurosporine, a protein kinase C inhibitor. Hence, small stress proteins are novel regulators that are able to block apoptosis induced by different pathways.