p21 is necessary for the p53-mediated G1 arrest in human cancer cells.

TLDR

DNA‑damaging agents trigger a p53‑dependent G1 arrest, and p21WAF1/CIP1 has been proposed as a key effector of this checkpoint. To test this, the authors generated an isogenic set of human colon adenocarcinoma cell lines that differ only in their p21 status. Loss of p21 completely abolishes the p53‑mediated G1 arrest, confirming p21 as a critical mediator of p53’s tumor‑suppressive function.

Abstract

DNA-damaging agents induce a p53-dependent G1 arrest that may be critical for p53-mediated tumor suppression. It has been suggested that p21WAF1/CIP1, a cdk inhibitory protein transcriptionally regulated by p53, is an effector of this arrest. To test this hypothesis, an isogenic set of human colon adenocarcinoma cell lines differing only in their p21 status was created. The parental cell line underwent the expected cell cycle changes upon induction of p53 expression by DNA damage, but the G1 arrest was completely abrogated in p21-deficient cells. These results unambiguously establish p21 as a critical mediator of one well-documented p53 function and have important implications for understanding cell cycle checkpoints and the mechanism(s) through which p53 inhibits human neoplasia.