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Tuesday, May 5, 2020

Role Of Caspase 3 And Other Important Proteins †Free Samples

Question: Discuss about the Role Of Caspase 3 And Other Important Proteins Such As The Inhibitors And The Promoters In The Process Of Apoptosis. Answer: Apoptosis is considered as a crucial physiological process that accounts for programmed cell death whereby elimination of the dead cells takes place by means of fragmentation into membrane bound particles that are eventually phagocytized by other cells. It is a stringently regulated genetic process and is triggered due to presence or absence of certain stimuli. In this context, caspases are referred to as family of endoproteases that is responsible for maintaining the homeostasis through regulation of cell death and inflammation. Depending upon their modes of action, these caspases have been classified into either initiator caspases or executioner caspases. Among these caspases, caspase 3 is considered as an executioner caspase that plays important role in cleaving and activating other executioner caspases thereby causing triggering of accelerated loop of caspase activation. Hallmarks of apoptosis related to chromatin condensation and DNA fragmentation is carried out by caspase 3 apa rt from performing functions related to dismantling of cells and formation of apoptotic bodies. Specific cleavage of key cellular proteins and loss of cell viability are also performed by caspase 3. Activation of caspase 3 has been found to be largely dependent upon the release of mitochondrial cytochrome c and function of initiator caspase, caspase 9 (McIlwain, Berger and Mak, 2015). Further studies have highlighted on the relative abundance of cellular proteins and their respective roles that account for cell death by apoptosis. Receptor-interacting serine/threonine protein kinase 3 (RIPK3) has been identified as a governing factor that represents the activation of caspase 8 and eventual death of cells by means of apoptosis. Another role played by this protein allows for induction of the pro-inflammatory cell death termed as necroptosis in conjunction with another protein labeled as RIPK1 in response to the death inducing TNF- family member (Newton et al. 2014). However, the regul ation of apoptosis has been studied to be largely dependent upon and determined by the relative distribution of the pro-apoptotic and anti-apoptotic proteins that act as promoters and inhibitors respectively. In this regard, the physiological control exerted by the BCL2 protein family has been recognized to be vital for depicting the commitment of cells towards apoptosis through setting up of a threshold due to interplay among the members of the protein family. The BH3 domain subset of the BCL2 protein has been found to promote apoptosis through interaction of its components such as Bim, Bid, BAD and others. Other members of BCL2 family are held responsible for initiating the Bax/Bak dependent apoptosis in the mitochondria (Czabotar et al. 2014). Further research conducted in this context, confirmed that a complex network of bimolecular interactions comprising of both transient as well as relatively stable associations account for the regulation of the BCL2 family proteins rather th an a mere rheostat mechanism of maintain the balance and sensitivity of the cells towards apoptotic stress. BAX and BCL-XL follow a dynamic pattern of interaction to exert their potential apoptotic influence over the cells by shuttling between the cytoplasm and the mitochondrial outer membrane (Volkmann et al. 2014). References Czabotar, P.E., Lessene, G., Strasser, A. and Adams, J.M., 2014. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy.Nature reviews. Molecular cell biology,15(1), p.49. McIlwain, D.R., Berger, T. and Mak, T.W., 2015. Caspase functions in cell death and disease.Cold Spring Harbor perspectives in biology,7(4). Newton, K., Dugger, D.L., Wickliffe, K.E., Kapoor, N., de Almagro, M.C., Vucic, D., Komuves, L., Ferrando, R.E., French, D.M., Webster, J. and Roose-Girma, M., 2014. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis.Science,343(6177), pp.1357-1360. Volkmann, N., Marassi, F.M., Newmeyer, D.D. and Hanein, D., 2014. The rheostat in the membrane: BCL-2 family proteins and apoptosis.Cell death and differentiation,21(2), p.206.

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