Old, new and emerging functions of caspases

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.