Science (American Association for the Advancement of Science), 2000-03, Vol.287 (5459), p.1824-1827
2000
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- Autor(en) / Beteiligte
- Titel
- DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
- Ist Teil von
- Science (American Association for the Advancement of Science), 2000-03, Vol.287 (5459), p.1824-1827
- Ort / Verlag
- Washington, DC: American Society for the Advancement of Science
- Erscheinungsjahr
- 2000
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- 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 G2phase 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.287.5459.1824Titel-ID: cdi_proquest_miscellaneous_743167751
- Format
- –
- Schlagworte
- Ageing, cell death, Animals, Antibodies, Apoptosis, Ataxia Telangiectasia Mutated Proteins, Biological and medical sciences, Cell cycle, Cell Cycle Proteins, Cell lines, Cell physiology, Checkpoint Kinase 2, Chk2 protein, Deoxyribonucleic acid, DNA, DNA Damage, DNA-Binding Proteins, Fundamental and applied biological sciences. Psychology, G1 Phase, G2 Phase, Gamma Rays, Gene Expression Regulation, Gene Targeting, Genes, p53, Genes, Tumor Suppressor, Genetics, Humans, Interphase, Irradiation, Mdm2 protein, Mice, Molecular and cellular biology, Nuclear Proteins, Phosphorylation, Phosphoserine - metabolism, Protein Kinases, Protein-Serine-Threonine Kinases - metabolism, Proteins, Proto-Oncogene Proteins - metabolism, Proto-Oncogene Proteins c-mdm2, Rodents, Stem Cells - cytology, Stem Cells - metabolism, Stimuli, T lymphocytes, T-Lymphocytes - cytology, Thymocytes, Transcription, Genetic, Tumor Suppressor Protein p53 - metabolism, Tumor Suppressor Proteins