DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
Copyright policy )DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting. Chk2 −/− embryonic stem cells failed to maintain γ-irradiation–induced arrest in the G 2 phase of the cell cycle. Chk2 −/− thymocytes were resistant to DNA damage–induced apoptosis. Chk2 −/− cells were defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to γ irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to γ irradiation. Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.
- Baylor College of Medicine United States
- Howard Hughes Medical Institute United States
- University of Toronto Canada
- Amgen (Canada) Canada
- Amgen (United States) United States
G2 Phase, G1 Phase, Nuclear Proteins, Apoptosis, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Genes, p53, DNA-Binding Proteins, Checkpoint Kinase 2, Mice, Phosphoserine, Gene Expression Regulation, Gamma Rays, Gene Targeting, Animals, Humans, Genes, Tumor Suppressor, Phosphorylation, Interphase, DNA Damage
G2 Phase, G1 Phase, Nuclear Proteins, Apoptosis, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Genes, p53, DNA-Binding Proteins, Checkpoint Kinase 2, Mice, Phosphoserine, Gene Expression Regulation, Gamma Rays, Gene Targeting, Animals, Humans, Genes, Tumor Suppressor, Phosphorylation, Interphase, DNA Damage
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