Graf Dirk, Bode Johannes G, Häussinger Dieter
Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University, Düsseldorf, Germany.
Arch Biochem Biophys. 2007 Jun 15;462(2):162-70. doi: 10.1016/j.abb.2007.03.029. Epub 2007 Apr 10.
In addition to their established functions in programmed cell death, there is increasing evidence that caspases contribute to several other cellular processes beside of apoptosis. So-called "dependence receptors" represent a group of receptors, which derive from different protein families, but are functionally linked by their capability to regulate cell survival in presence of their respective ligands thereby preserving cellular homeostasis. In the absence of their ligands these receptors are cleaved by caspases thereby releasing pro-apoptotic receptor fragments (e.g. rearranged during transfection [RET]) or permitting the exposure of death domains, which were masked before through other receptor domains (e.g. deleted in colorectal carcinoma [DCC]). Apart from these, there are other plasma membrane receptors such as the epidermal growth factor receptor, which have been identified as substrates of caspases. In terms of signal-transduction, caspase-mediated cleavage of these receptors blocks ligand-induced activation of their intracellular signalling. It is hypothesized that this might be another mechanism, whereby caspases trigger cell toxicity through shut-down of survival signals.
除了在程序性细胞死亡中已确定的功能外，越来越多的证据表明，半胱天冬酶除了参与细胞凋亡外，还参与其他几种细胞过程。所谓的“依赖受体”代表了一组受体，它们来自不同的蛋白质家族，但在功能上通过其在各自配体存在时调节细胞存活从而维持细胞稳态的能力而联系在一起。在没有其配体的情况下，这些受体被半胱天冬酶切割，从而释放促凋亡受体片段（例如在转染期间重排的[RET]）或允许暴露之前被其他受体结构域掩盖的死亡结构域（例如在结直肠癌中缺失的[DCC]）。除此之外，还有其他质膜受体，如表皮生长因子受体，已被确定为半胱天冬酶的底物。就信号转导而言，半胱天冬酶介导的这些受体切割会阻断配体诱导的细胞内信号激活。据推测，这可能是半胱天冬酶通过关闭存活信号触发细胞毒性的另一种机制。
