Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea.
DNA Cell Biol. 2012 Jan;31(1):1-7. doi: 10.1089/dna.2011.1323. Epub 2011 Nov 11.
Caspase-2 is an enigmatic caspase that is now increasingly being associated with certain types of cell death in cells exposed to cytotoxic agents. It is now known that in some cases of cell stress, such as DNA damage, activation of this caspase is triggered, sometimes in the absence of activation of both the intrinsic and extrinsic pathways of apoptosis. Part of the reason for this enigma has been lack of a suitable stimulus for this caspase, and with the discovery of DNAzyme 13 (Dz13), a potent oligonucleotide-based caspase-2 activator, much more can now be elucidated. For instance, one thing that could be unraveled is whether caspase-8 and Fas (CD95)-associated protein with death domain are indeed involved in caspase-2 activation as part of the death-inducing signaling complex. It is also becoming apparent that this enigmatic caspase may be important in the mechanisms behind which chemotherapeutic agents inhibit tumor cell growth. A better understanding of the true biological effects of this enzyme may indeed lead to more effective ways of managing tumors clinically. This review article briefly examines the different compounds capable of inducing activation of caspase-2 and proposes Dz13 as one that will be valuable for evaluation of the biological functions of caspase-2.
半胱天冬酶-2 是一种神秘的半胱天冬酶，现在越来越多地与暴露于细胞毒性药物的细胞中的某些类型的细胞死亡相关联。现在已知，在某些细胞应激情况下，如 DNA 损伤，这种半胱天冬酶的激活会被触发，有时在内在和外在凋亡途径的激活都不存在的情况下。造成这种神秘性的部分原因是缺乏这种半胱天冬酶的合适刺激物，而随着 DNA 酶 13（Dz13）的发现，一种有效的基于寡核苷酸的半胱天冬酶-2 激活剂，现在可以阐明更多的内容。例如，可以揭示的一件事是，半胱天冬酶-8 和 Fas（CD95）相关死亡结构域蛋白是否确实参与了半胱天冬酶-2 的激活，作为诱导死亡信号复合物的一部分。现在也越来越明显的是，这种神秘的半胱天冬酶可能在化疗药物抑制肿瘤细胞生长的机制中很重要。更好地了解这种酶的真正生物学效应可能确实会导致更有效的临床肿瘤管理方法。这篇综述文章简要地检查了能够诱导半胱天冬酶-2 激活的不同化合物，并提出 Dz13 是一种评估半胱天冬酶-2 生物学功能的有价值的化合物。
