The role of the apoptosome in the activation of procaspase-9
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2013, Vol 67, Issue 0
Abstract
Apoptosis, also called programmed cell death, is a physiological process that causes a numberof morphological and biochemical changes, occurring in the cell and leading to its death.Along with the processes of proliferation, differentiation and maturation, it is responsible forcontrolling the amount and types of cells, removing those that are unnecessary or dangerousfor the organism. The most important enzymes involved in apoptosis are caspases, which hydrolyzethe structural and functional proteins, ultimately leading to cell death. The caspasesare synthesized in the cell as inactive zymogens and have to be activated in order to perform their functions. Two pathways lead to the activation of caspases: the extrinsic pathway associatedwith membrane receptors and their ligands, and the intrinsic pathway dependent onmitochondria. The central element in the mitochondrial pathway is a special protein complex,the apoptosome, which enables and facilitates the activation of procaspase 9. Apaf-1, cytochromec and dATP/ATP are needed to form the apoptosome. Active apoptosomes arise onlyin response to apoptotic agents. There are many factors regulating apoptosome formation inphysiological conditions. It was shown that disorders in apoptosome formation have greatimportance in the pathogenesis of cancer and the occurrence of resistance to chemotherapy.Therefore, research continues on finding compounds which are able to induce or inhibit theformation of the apoptosome. The results of this research will have great importance for thetreatment of cancers or diseases resulting from an excessively prolonged process of apoptosis.In this paper the general characteristics of the apoptosome, its role and mechanism of formationare presented. Additional information is given on the regulation of its activity and on therole of disturbance of apoptosome activity in cancerogenesis and chemoresistance. Particularattention is paid to those compounds that are able to influence the formation and activationof the apoptosome, and may in future be interesting therapeutic tools.
Authors and Affiliations
Łukasz Marek
Keywords
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