| First Author | Hirao A | Year | 2000 |
| Journal | Science | Volume | 287 |
| Issue | 5459 | Pages | 1824-7 |
| PubMed ID | 10710310 | Mgi Jnum | J:60946 |
| Mgi Id | MGI:1354114 | Doi | 10.1126/science.287.5459.1824 |
| Citation | Hirao A, et al. (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2 [see comments]. Science 287(5459):1824-7 |
| abstractText | 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 gamma-irradiation-induced arrest in the G2 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 gamma irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to gamma 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. |
