AI Article Synopsis
- Chk2 is a key player in cellular responses to genotoxic stress, particularly activated by ionizing radiation, which leads to G2 phase cell cycle arrest.
- It phosphorylates and stabilizes the tumor suppressor protein p53, suggesting a cooperative role between Chk2 and p53 in responding to DNA damage.
- In a study using p53-deficient mice, Chk2 expression was significantly lower in certain organs (heart, kidney, lung, liver) compared to p53-positive mice, indicating that p53 regulates Chk2 expression in a tissue-specific way.
Article Abstract
Chk2 (Checkpoint kinase 2) is emerging as a critical mediator of genotoxic stress and diverse cellular responses. Upon ionizing radiation, Chk2 is activated to phosphorylate Cdc25C, leading to G2 phase arrest. p53 has been reported as another substrate of Chk2. Chk2 phosphorylates and stabilizes p53 in response to ionizing radiation. Previous studies found that p53 regulates the Chk2 homologue Chk1 expression both in vitro and in vivo. Using the p53-deficient mouse model, here we demonstrate by immunohistochemistry, Western blot analysis, and RT-PCR that mChk2 expression is reduced in the heart, kidney, lung, and liver of p53(-/-) mice compared to p53(+/+) controls. Similar Chk2 expression was observed in the brain, skin, spleen, and testis in p53(+/+) and p53(-/-) mice. These data indicate that p53 regulates Chk2 expression in a tissue-specific manner.
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| http://dx.doi.org/10.1016/s0014-4800(03)00088-1 | DOI Listing |
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