Shalini S, Dorstyn L, Dawar S, Kumar S
Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia.
Cell Death Differ. 2015 Apr;22(4):526-39. doi: 10.1038/cdd.2014.216. Epub 2014 Dec 19.
Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.
半胱天冬酶是在细胞凋亡中具有明确作用的蛋白酶。然而，越来越多的证据表明半胱天冬酶在细胞凋亡之外具有多种功能。半胱天冬酶-1和半胱天冬酶-11在炎症以及通过细胞焦亡介导炎症性细胞死亡中发挥作用。同样，半胱天冬酶-8在细胞死亡中具有双重作用，介导受体介导的细胞凋亡，在其缺失时则介导坏死性凋亡。半胱天冬酶-8还在成年T细胞群体的维持和体内平衡中发挥作用。半胱天冬酶-3在组织分化、再生和神经发育中具有重要作用，其方式独特且不涉及任何细胞凋亡活性。其他几种半胱天冬酶已显示出抗肿瘤作用。其中值得注意的是半胱天冬酶-2、-8和-14。然而，在某些类型的肿瘤中半胱天冬酶-2和-8表达的增加也与促进肿瘤发生有关。肿瘤细胞中半胱天冬酶-3水平的升高会导致细胞凋亡并分泌旁分泌因子，从而促进周围正常组织的代偿性增殖、肿瘤细胞再增殖，并为有效的治疗策略带来障碍。除此之外，半胱天冬酶-2已成为一种独特的半胱天冬酶，在维持基因组稳定性、代谢、自噬和衰老方面具有潜在作用。本综述重点关注哺乳动物半胱天冬酶的一些研究较少且新出现的功能。
