P21 IS NECESSARY FOR THE P53-MEDIATED G(1) ARREST IN HUMAN CANCER-CELLS

DNA-damaging agents induce a p53-dependent G(1) arrest that may be cri tical for p53-mediated tumor suppression. It has been suggested that p 21(WAF1/CIP1), a cdk inhibitory protein transcriptionally regulated by p53, is an effector of this arrest. To test this hypothesis, an isoge nic set of human colon adenocarcinoma cell lines differing only in the ir p21 status was created. The parental cell line underwent the expect ed cell cycle changes upon induction of p53 expression by DNA damage, but the G(1) arrest was completely abrogated in p21-deficient cells. T hese results unambiguously establish p21 as a critical mediator of one well-documented p53 function and have important implications for unde rstanding cell cycle checkpoints and the mechanism(s) through which p5 3 inhibits human neoplasia.