CHEK2 and breast carcinoma: While Chk2 activates multiple downstream targets in addition to p53, and the p53 protein may be activated through multiple post-transcriptional events [17], the finding that CHEK2 mutations may substitute for TP53 mutations as a cause of chemo-resistance indicates Chk2 phosphorylation of the p53 protein to play a pivotal role executing cell death in response to anthracycline therapy in breast cancer.