Bruey J M, Ducasse C, Bonniaud P, Ravagnan L, Susin S A, Diaz-Latoud C, Gurbuxani S, Arrigo A P, Kroemer G, Solary E, Garrido C
INSERM U-517, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France.
Nat Cell Biol. 2000 Sep;2(9):645-52. doi: 10.1038/35023595.
Mammalian cells respond to stress by accumulating or activating a set of highly conserved proteins known as heat-shock proteins (HSPs). Several of these proteins interfere negatively with apoptosis. We show that the small HSP known as Hsp27 inhibits cytochrome-c-mediated activation of caspases in the cytosol. Hsp27 does not interfere with granzyme-B-induced activation of caspases, nor with apoptosis-inducing factor-mediated, caspase-independent, nuclear changes. Hsp27 binds to cytochrome c released from the mitochondria to the cytosol and prevents cytochrome-c-mediated interaction of Apaf-1 with procaspase-9. Thus, Hsp27 interferes specifically with the mitochondrial pathway of caspase-dependent cell death.
哺乳动物细胞通过积累或激活一组被称为热休克蛋白(HSPs)的高度保守的蛋白质来应对压力。其中几种蛋白质对细胞凋亡有负向干扰作用。我们发现,名为Hsp27的小分子热休克蛋白可抑制细胞溶质中细胞色素c介导的半胱天冬酶激活。Hsp27既不干扰颗粒酶B诱导的半胱天冬酶激活,也不干扰凋亡诱导因子介导的、不依赖半胱天冬酶的核变化。Hsp27与从线粒体释放到细胞溶质中的细胞色素c结合,并阻止细胞色素c介导的凋亡蛋白酶激活因子-1与procaspase-9的相互作用。因此,Hsp27特异性地干扰了依赖半胱天冬酶的细胞死亡的线粒体途径。