914 results found
    1. Neuroscience

    Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1/Mef2 activation, leading to neurodegeneration

    Kuchuan Chen et al.
    In Drosophila, the loss of Frataxin causes iron accumulation in the nervous system, which in turn enhances sphingolipid synthesis and activation of PDK1 and Mef2, which leads to neurodegeneration.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism

    Huasong Lu et al.
    A new potent and selective CDK9 inhibitor induces the expression of the proto-oncogene MYC via a mechanism that depends on the bromodomain protein BRD4.
    1. Biochemistry and Chemical Biology

    Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation

    Lu Lv et al.
    High-throughput phenotypic screening followed by unbiased target identification reveals a new molecular glue HQ461 that induces CDK12-DDB1 interaction to promote degradation of Cyclin K via the ubiquitin proteasome system.
    1. Computational and Systems Biology

    CDK9-dependent RNA polymerase II pausing controls transcription initiation

    Saskia Gressel et al.
    CDK9 inhibition in human cells uncovers that Pol II pause duration regulates the frequency of productive transcription initiation.
    1. Neuroscience

    Loss of Frataxin activates the iron/sphingolipid/PDK1/Mef2 pathway in mammals

    Kuchuan Chen et al.
    The iron/sphingolipid/PDK1/Mef2 pathway is activated in mammals upon loss of Frataxin.
    1. Cell Biology

    Stress-mediated exit to quiescence restricted by increasing persistence in CDK4/6 activation

    Hee Won Yang et al.
    Application of a live-cell reporter for CDK4/6 activity reveals rapid activity changes and reversibility in the cell-cycle entry signaling program.
    1. Developmental Biology

    Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila

    Amrutha Kizhedathu et al.
    ATR/Chk1 contribute to G2 arrest in developing tracheoblasts, and arrest in G2 facilitates cellular and hypertrophic organ growth.
    1. Chromosomes and Gene Expression

    Cdc7 activates replication checkpoint by phosphorylating the Chk1-binding domain of Claspin in human cells

    Chi-Chun Yang et al.
    Cdc7 and CK1g1 independently and additively phosphorylate the Chk1-binding domain of claspin to activate replication checkpoint with differential contribution of each kinase in different cell types.
    1. Cell Biology

    Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk

    Olga Afonso et al.
    Quantitative live-cell microscopy and molecular perturbations in Drosophila and human cells reveal a crosstalk between molecular 'rulers' (Aurora B) and 'clocks' (Cdk1) that coordinates mitotic exit in space and time.
    1. Cancer Biology
    2. Cell Biology

    The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells

    Shaheen Kabir et al.
    Targeting the CRL5 ubiquitin ligase complex in combination with CDK9 or MCL1 inhibition could combat innate and acquired resistance of cancer cells to MCL1-targeting therapeutics.

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