Overview:

CHK2 is a highly conserved tumor suppressor protein that is activated in response to DNA damage in an ATM-dependent manner (1). Activation of CHK2 is dependent on phosphorylation at sites including Thr68 (2). CHK2 controls cell cycle arrest, DNA repair and apoptosis through activation of DNA damage response proteins such as p53 and BRCA1. Expressing wild-type CHK2 leads to increased p53 stabilization after DNA damage, whereas expression of a dominant-negative CHK2 mutant abrogates phosphorylation of p53, leading to decreased stability (3).

References:

1. Matsuoka, S. et al: Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science. 1998 Dec 4;282(5395):1893-7.

2. Li J. et al: Regulation of CHK2 by DNA-dependent protein kinase. J Biol Chem. 2005 Mar 25;280(12):12041-50.

3. Chehab NH. et al: Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev. 2000 Feb 1;14(3):278-88.