Waldman T, Kinzler K W, Vogelstein B
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Cancer Res. 1995 Nov 15;55(22):5187-90.
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.
DNA损伤剂可诱导p53依赖的G1期阻滞，这可能对p53介导的肿瘤抑制至关重要。有人提出，p21WAF1/CIP1是一种受p53转录调控的细胞周期蛋白依赖性激酶抑制蛋白，是这种阻滞的效应器。为了验证这一假设，构建了一组仅在p21状态上存在差异的同基因人类结肠腺癌细胞系。亲本细胞系在DNA损伤诱导p53表达后经历了预期的细胞周期变化，但在p21缺陷细胞中，G1期阻滞完全消除。这些结果明确地将p21确立为一种已被充分证明的p53功能的关键介质，对于理解细胞周期检查点以及p53抑制人类肿瘤形成的机制具有重要意义。
