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Publication - Professor Wendy Gibson

    Phosphorylation of eIF2α on Threonine 169 is not required for Trypanosoma brucei cell cycle arrest during differentiation

    Citation

    Avila, CCD, Peacock, L, Machado, FC, Gibson, WC, Schenkman, S, Carrington, M & Castilho, BA, 2016, ‘Phosphorylation of eIF2α on Threonine 169 is not required for Trypanosoma brucei cell cycle arrest during differentiation’. Molecular and Biochemical Parasitology, vol 205., pp. 16-21

    Abstract

    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 bloodstream 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 (eIF2α). The effect of eIF2α
    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 eIF2α in
    the life cycle of T. brucei, a cell line was made with a single
    eIF2α 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 eIF2α on threonine 169 is not necessary for the cell
    cycle arrest associated with these differentiation processes.

    Full details in the University publications repository