Garrido Carmen, Schmitt Elise, Candé Céline, Vahsen Nicola, Parcellier Arnaud, Kroemer Guido
INSERM U517, Faculty of Medicine, 21033 Dijon, France.
Cell Cycle. 2003 Nov-Dec;2(6):579-84.
Stress or heat shock proteins (HSPs) such as HSP27 and HSP70 are expressed in response to a wide variety of physiological and environmental insults including heat, reactive oxygen species or anticancer drugs. Their overexpression allows cells to survive to otherwise lethal conditions. Several different mechanisms may account for the cytoprotective activity of HSP27 and HSP70. First, both proteins are powerful chaperones. Second, both inhibit key effectors of the apoptotic machinery including the apoptosome, the caspase activation complex (both HSP27 and HSP70), and apoptosis inducing factor (only HSP70). Third, they both play a role in the proteasome-mediated degradation of apoptosis-regulatory proteins. HSP27 and HSP70 may participate in oncogenesis, as suggested by the fact that overexpression of heat shock proteins can increase the tumorigenic potential of tumor cells. The down-regulation or selective inhibition of HSP70 might constitute a valuable strategy for the treatment of cancer.
应激或热休克蛋白（HSPs），如HSP27和HSP70，会在多种生理和环境损伤因素的刺激下表达，这些损伤因素包括热、活性氧或抗癌药物。它们的过表达能使细胞在原本致命的条件下存活。HSP27和HSP70的细胞保护活性可能由几种不同机制导致。首先，这两种蛋白都是强大的分子伴侣。其次，它们都能抑制凋亡机制的关键效应器，包括凋亡小体、半胱天冬酶激活复合物（HSP27和HSP70均可抑制）以及凋亡诱导因子（只有HSP70能抑制）。第三，它们都在蛋白酶体介导的凋亡调节蛋白降解过程中发挥作用。热休克蛋白的过表达可增加肿瘤细胞的致瘤潜能，这表明HSP27和HSP70可能参与肿瘤发生。下调或选择性抑制HSP70可能是一种有价值的癌症治疗策略。
