Caspase-mediated cleavage of p21Wafl/Cip1 converts cancer cells from growth arrest to undergoing apoptosis

The cyclin-dependent kinase inhibitor p21(Waf1/Cip1) is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of (DHVDL)-L-112 down arrow during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G(1) phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells.