FEBS Letters · 2001 · 32 citations · 28 references
Life SciencesCell BiologyMolecular BiologyCell CycleMolecular Cell BiologySignal TransductionCell Cycle ControlCell Cycle SignalingCell-cycle ArrestCell-cycle CheckpointsCell-cycle RegulationDna Damage SignalingCdc25 Phosphatase SignalingCell-cycle Checkpoint RegulationCheckpoint Kinase 2 SignalingCheckpoint Kinase SignalingCheckpoint Pathway ActivationDna Damage Checkpoint ActivationDna Damage Checkpoint KinasesDna Damage Checkpoint Signaling
The bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment. In contrast to what is observed with other DNA damaging agents, we demonstrate that the activation of CHK2 can only take place during S-phase. Use of wortmannin and caffeine suggests that this effect is not dependent on ATM but rather on another as yet unidentified PI3 kinase family member. These results confirm that the CDT is therefore responsible for specific genomic injuries that block cell proliferation by activating a cell cycle checkpoint.
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Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Christine E. Canman, Dae‐Sik Lim, Karlene A. Cimprich et al. · Science · 1998 · 2.1K citations
Enhanced Phosphorylation of p53 by ATM in Response to DNA Damage
Sharon Banin, Lilach Moyal, Sheau-Yann Shieh et al. · Science · 1998 · 1.8K citations
Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Satomi Matsuoka · 1998 · 1.3K citations