3,368 results found
    1. Cancer Biology

    Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition

    Andrew L Hong et al.
    Faithful models of RMC require SMARCB1 loss for survival, and genetic and small-molecule screens identify inhibition of the ubiquitin-proteasome system (UPS) as a potential therapeutic approach for SMARCB1 deficient cancers.
    1. Microbiology and Infectious Disease

    A novel central nervous system-penetrating protease inhibitor overcomes human immunodeficiency virus 1 resistance with unprecedented aM to pM potency

    Manabu Aoki et al.
    GRL-142 is an HIV protease inhibitor with a unique structure and atto-to-picomolar potency against a wide range of HIV strains.
    1. Cell Biology

    Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

    Diego Acosta-Alvear et al.
    The nodes of the cytosolic proteostasis network can control sensitivity to proteasome inhibitors and decreased levels of the 19S proteasomal regulator can lead to increased resistance to inhibitors.
    1. Cell Biology

    p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition

    Senthil K Radhakrishnan et al.
    The enzyme p97/VCP regulates the activity of the transcription factor Nrf1 to promote increased transcription of genes that encode proteasome subunits following inhibition of the proteasome.
    1. Structural Biology and Molecular Biophysics

    Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition

    Corey M Dambacher et al.
    Within the isolated lid sub-complex of the proteasome, a finely tuned network of interactions maintains the deubiquitinase in an inhibited conformation; dramatic rearrangements of the lid subunits upon incorporation into the holoenzyme lead to the deubiquitinase’s activation.
    1. Neuroscience

    α-synuclein strains that cause distinct pathologies differentially inhibit proteasome

    Genjiro Suzuki et al.
    One α-synuclein strain inhibited proteasome activity and induced apparent pathologies, while the other did not, indicating a strain-dependent toxicity of α-synuclein aggregates, which support a prion-like behavior of α-synuclein.
    1. Neuroscience

    The switch-like expression of heme-regulated kinase 1 mediates neuronal proteostasis following proteasome inhibition

    Beatriz Alvarez-Castelao et al.
    In neurons, inhibition of the proteasome results in feedback inhibition of protein synthesis, mediated by heme-regulated kinase 1, which is optimized to act as both a sensor and an effector.
    1. Cell Biology

    Compromising the 19S proteasome complex protects cells from reduced flux through the proteasome

    Peter Tsvetkov et al.
    Reducing the expression of 19S subunits shifts the ratio of 20S/26S proteasome complexes and provides a powerful survival advantage in the face of lethal proteasome inhibition.
    1. Biochemistry and Chemical Biology

    The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction

    Shun Koizumi et al.
    Peptidase activity of DDI2 is required to activate Nrf1 in order to enable proteasome recovery in response to proteasome inhibition.
    1. Plant Biology
    2. Evolutionary Biology

    Herbivory-induced volatiles function as defenses increasing fitness of the native plant Nicotiana attenuata in nature

    Meredith C Schuman et al.
    A 2-year field study has demonstrated that volatile compounds produced by plants when they are attacked by herbivores act as defenses by attracting predators to the herbivores and increasing the reproduction of the plants.

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