Tissue-specific regulation of checkpoint kinase 2 expression by p53.
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.
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D064447:Checkpoint Kinase 2; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006321:Heart / Q000502:physiology; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases