Tissue-Specific Regulation of Chk1 Expression by p53

Abstract The regulation of Chk1, a critical protein kinase involved in G 2 phase arrest, has been a subject of recent research. Chk1 phosphorylates tumor suppressor p53 at multiple sites, while p53 has been shown to downregulate Chk1 expression under stress conditions in vitro , suggesting negative feedback between the two checkpoint proteins. Using the p53 knockout mouse model, we demonstrate by Western blot and immunohistochemistry that mChk1 expression is induced in spleen, thymus, and dermal fibroblasts and is reduced in lung and testis in p53 −/− mice compared to p53 +/+ controls. The mChk1 protein was undetectable in heart, kidney, and skin, whereas abundant expression was observed in brain and liver in both p53 +/+ and p53 −/− mice. These data indicate that p53 regulates Chk1 expression in a tissue-specific manner.