EVOLUTIONARY AND BIOCHEMICAL CHARACTERIZATION OF EFFECTOR CASPASES

Abstract

Caspases are an ancient class of cysteine-dependent aspartate-specific proteases that control apoptosis, responsible for cell differentiation, and maintain cellular homeostasis in multicellular organisms. Dysregulation of caspase functions leads to many human diseases, including cancer and neurological disorders. Due to the involvement of caspases in several diseases, it is crucial to understand how they are regulated. Extant human caspases have been studied extensively for over two decades. However, the success in the development of therapeutics against caspase dysfunctions has very little success to date. Hence, the evolutionary approaches for studying caspases could help understand their structure and function and the overall protein evolution. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens that must be activated to gain full activity. The protein structures and substrate specificity are conserved through millions of years of evolution, and some regulatory features are ancient, and therefore common, while other features are modern and cluster-specific.