86 results found
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski et al.
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Fail-safe control of translation initiation by dissociation of eIF2α phosphorylated ternary complexes

    Martin D Jennings et al.
    Phosphorylated translation initiation factor eIF2, a potent inhibitor of protein synthesis in eukaryotic cells, is also inhibitory to protein synthesis when bound to GTP and initiator tRNA broadening the reach and immediacy of eIF2-mediated control.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes

    Yao Liang Wong et al.
    Vanishing White Matter Disease mutations compromise the function of the essential translation initiation factor eIF2B by destabilizing the holoenzyme, and the small molecule ISRIB reverses their pathogenic effect by promoting complex formation.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Interface between 40S exit channel protein uS7/Rps5 and eIF2α modulates start codon recognition in vivo

    Jyothsna Visweswaraiah, Alan G Hinnebusch
    The small subunit ribosomal protein uS7/Rps5 interacts with translation initiation factor eIF2α to stabilize first the open, and then the closed conformation of the pre-initiation complex to promote accurate start codon selection in vivo.
    1. Cell Biology
    2. Neuroscience

    The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly

    Carmela Sidrauski et al.
    Building on previous work which showed that the small molecule ISRIB potently blocks the integrated stress response (Sidrauski et al., 2013), we report on ISRIB's remarkable specificity and fast action in vivo, underscoring its proposed direct effect on translation.
    1. Neuroscience

    eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons

    Andon N Placzek et al.
    Building on previous work (Huang et al., 2016), we show that translational control by p-eIF2α is a defense mechanism that prevents persistent cocaine-induced synaptic synaptic potentiation underlying compulsive drug seeking.
    1. Neuroscience

    GSK3β regulates AKT-induced central nervous system axon regeneration via an eIF2Bε-dependent, mTORC1-independent pathway

    Xinzheng Guo et al.
    The AKT-GSK3β-eIF2Bε signaling module plays a key role in promoting axon regeneration in the adult mammalian central nervous system.
    1. Neuroscience

    Translational control of nicotine-evoked synaptic potentiation in mice and neuronal responses in human smokers by eIF2α

    Andon N Placzek et al.
    An evolutionarily conserved mechanism involving translational control by p-eIF2α underlies vulnerability to nicotine addiction.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    PPP1R15A-mediated dephosphorylation of eIF2α is unaffected by Sephin1 or Guanabenz

    Ana Crespillo-Casado et al.
    The notion that the drug-like small molecule Sephin1 protects against protein misfolding by selectively disrupting a cellular phosphatase is refuted.
    1. Neuroscience

    Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine

    Wei Huang et al.
    Vulnerability to cocaine addiction during adolescence depends on translational control.

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