Gabai V L, Meriin A B, Yaglom J A, Volloch V Z, Sherman M Y
Boston Biomedical Research Institute, MA, USA.
FEBS Lett. 1998 Oct 30;438(1-2):1-4. doi: 10.1016/s0014-5793(98)01242-3.
Cell protection from stresses by the major heat shock protein Hsp72 was previously attributed to its ability to prevent aggregation and to accelerate refolding of damaged proteins. This repair function of Hsp72 may play an important role in cell survival after extremely harsh protein damaging treatments leading to necrotic cell death. On the other hand, protein repair function of Hsp72 cannot explain how it protects cells from stresses which do not cause direct protein damage, e.g. some genotoxic agents. These stresses kill cells through activation of apoptosis, and Hsp72 increases cell survival by interfering with the apoptotic program. Recently it has been found that Hsp72 mediates suppression of a stress-activated protein kinase, JNK, an early component of stress-induced apoptotic signalling pathway. This finding provides the basis for the anti-apoptotic activity of Hsp72. These observations can explain increased stress sensitivity of aged cells in which compromised inducibility of Hsp72 leads to a loss of control of JNK activation by stresses and subsequently to a higher rate of apoptotic death.
主要热休克蛋白Hsp72对细胞的应激保护作用，以前被认为归因于其防止蛋白质聚集以及加速受损蛋白质重新折叠的能力。Hsp72的这种修复功能，可能在导致坏死性细胞死亡的极其严苛的蛋白质损伤处理后，对细胞存活起到重要作用。另一方面，Hsp72的蛋白质修复功能无法解释它如何保护细胞免受不会造成直接蛋白质损伤的应激，例如某些基因毒性剂。这些应激通过激活凋亡杀死细胞，而Hsp72通过干扰凋亡程序提高细胞存活率。最近发现，Hsp72介导对应激激活蛋白激酶JNK的抑制，JNK是应激诱导的凋亡信号通路的早期组成部分。这一发现为Hsp72的抗凋亡活性提供了基础。这些观察结果可以解释衰老细胞应激敏感性增加的现象，其中Hsp72诱导能力受损导致应激对JNK激活失去控制，进而导致更高的凋亡死亡率。
