Sreedhar Amere Subbarao, Csermely Peter
Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest, Hungary.
Pharmacol Ther. 2004 Mar;101(3):227-57. doi: 10.1016/j.pharmthera.2003.11.004.
Heat shock proteins (Hsp) form the most ancient defense system in all living organisms on earth. These proteins act as molecular chaperones by helping in the refolding of misfolded proteins and assisting in their elimination if they become irreversibly damaged. Hsp interact with a number of cellular systems and form efficient cytoprotective mechanisms. However, in some cases, wherein it is better if the cell dies, there is no reason for any further defense. Programmed cell death is a widely conserved general phenomenon helping in many processes involving the reconstruction of multicellular organisms, as well as in the elimination of old or damaged cells. Here, we review some novel elements of the apoptotic process, such as its interrelationship with cellular senescence and necrosis, as well as bacterial apoptosis. We also give a survey of the most important elements of the apoptotic machinery and show the various modes of how Hsp interact with the apoptotic events in detail. We review caspase-independent apoptotic pathways and anoikis as well. Finally, we show the emerging variety of pharmacological interventions inhibiting or, just conversely, inducing Hsp and review the emergence of Hsp as novel therapeutic targets in anticancer protocols.
热休克蛋白（Hsp）构成了地球上所有生物中最古老的防御系统。这些蛋白质作为分子伴侣，帮助错误折叠的蛋白质重新折叠，并在它们受到不可逆损伤时协助将其清除。热休克蛋白与许多细胞系统相互作用，并形成有效的细胞保护机制。然而，在某些情况下，如果细胞死亡更好，那么就没有进一步防御的理由。程序性细胞死亡是一种广泛保守的普遍现象，有助于许多涉及多细胞生物重建的过程，以及清除衰老或受损细胞。在这里，我们综述了凋亡过程的一些新元素，例如它与细胞衰老和坏死的相互关系，以及细菌凋亡。我们还概述了凋亡机制的最重要元素，并详细展示了热休克蛋白与凋亡事件相互作用的各种方式。我们也综述了不依赖半胱天冬酶的凋亡途径和失巢凋亡。最后，我们展示了抑制或相反诱导热休克蛋白的各种新兴药理学干预措施，并综述了热休克蛋白作为抗癌方案中新的治疗靶点的出现。
