Phosphorylation of eif2 alpha on threonine 169 is not required for trypanosoma brucei cell cycle arrest during differentiation
Data
2016
Autores
Avila, Carla Cristi D. C. 
Machado, Fabricio Castro
Schenkman, Sergio
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The trypanosome life cycle consists of a series of developmental forms each adapted to an environment in the relevant insect and/or mammalian host. The differentiation process from the mammalian blood-stream form to the insect-midgut procyclic form in Trypanosoma brucei occurs in two steps in vivo. First proliferating 'slender' bloodstream forms differentiate to non-dividing 'stumpy' forms arrested in G1. Second, in response to environmental cues, stumpy bloodstream forms re-enter the cell cycle and start to proliferate as procyclic forms after a lag during which both cell morphology and gene expression are modified. Nearly all arrested cells have lower rates of protein synthesis when compared to the proliferating equivalent. In eukaryotes, one mechanism used to regulate the overall rate of protein synthesis involves phosphorylation of the alpha subunit of initiation factor eIF2 (eIF2 alpha). The effect of elF2 alpha phosphorylation is to prevent the action of eIF2B, the guanine nucleotide exchange factor that activates eIF2 for the next rounds of initiation. To investigate the role of the phosphorylation of eIF2 alpha in the life cycle of T. brucei, a cell line was made with a single eIF2 alpha gene that contained the phosphorylation site, threonine 169, mutated to alanine. These cells were capable of differentiating from proliferating bloodstream form cells into arrested stumpy forms in mice and into procyclic forms in vitro and in tsetse flies. These results indicate that translation attenuation mediated by the phosphorylation of eIF2 alpha on threonine 169 is not necessary for the cell cycle arrest associated with these differentiation processes. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.orgilicenses/by/4.0/).
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Molecular And Biochemical Parasitology. Amsterdam, v. 205, n. 43132, p. 16-21, 2016.