PubMed · 1999 · 103 citations · 22 references
Life SciencesCancer BiologyOncologyApoptosisCell DivisionMolecular OncologyApoptosis In CancerCell Cycle ControlCell Cycle SignalingCell-cycle CheckpointsDna Damage SignalingDna Damage-induced ApoptosisCheckpoint Kinase InhibitionCheckpoint Kinase SignalingDna Damage Checkpoint ActivationDna Damage Checkpoint KinasesDna Damage Checkpoint SignalingDna Damage-induced Cell DeathG2 Checkpoint ArrestP53-mediated Cell Death
We devised two short peptides corresponding to amino acids 211-221 of human Cdc25C fused with a part of HIV1-TAT. These peptides inhibited hChk1 and Chk2/HuCds1 kinase activity in vitro and specifically abrogated the G2 checkpoint in vivo. These peptides sensitized p53-defective cancer cell lines to DNA-damaging agent to death without obvious cytotoxic effect on normal cells. Our results clearly indicate that the specific abrogation of the cell cycle G2 checkpoint is a feasible strategy for cancer therapy, and hChk1 and Chk2/HuCds1 are proper targets for that purpose.
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Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Satomi Matsuoka · 1998 · 1.3K citations