Chen Xi, Zhang Wei, Gao Yun Fei, Su Xiao Qin, Zhai Zhong He
College of Life Sciences, Peking University, Beijing, China.
Cell Res. 2002 Sep;12(3-4):229-33. doi: 10.1038/sj.cr.7290129.
P21(Waf1/Cip1) is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21(Waf1/Cip1) involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidence for a link between p21(Waf1/Cip1) and cellular senescence. While in murine cells, the role of p21(Waf1/Cip1) is indefinite. We explored this issue using NIH3T3 cells with inducible p21(Waf1/Cip1) expression. Induction of p21(Waf1/Cip1) triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features, such as enlarged and flattened cellular shape, specific to the senescence phenotype. We also showed that p21(Waf1/Cip1)-transduced NIH3T3 cells expressed beta-galactosidase activity at pH 6.0, which is known to be a marker of senescence. Our results suggest that p2l(Waf1/Cip1) can also induce senescence-like changes in murine cells.
P21（Waf1/Cip1）是一种有效的细胞周期蛋白依赖性激酶抑制剂。作为p53的下游介质，P21（Waf1/Cip1）参与细胞周期停滞、分化和凋亡。先前在人类细胞中的研究为P21（Waf1/Cip1）与细胞衰老之间的联系提供了证据。而在鼠细胞中，P21（Waf1/Cip1）的作用尚不明确。我们使用可诱导P21（Waf1/Cip1）表达的NIH3T3细胞来探究这个问题。P21（Waf1/Cip1）的诱导引发了G1期生长停滞，并且NIH3T3-p21细胞表现出衰老表型特有的形态学特征，如细胞形状增大和平坦化。我们还表明，转导了P21（Waf1/Cip1）的NIH3T3细胞在pH 6.0时表达β-半乳糖苷酶活性，这是已知的衰老标志物。我们的结果表明，P21（Waf1/Cip1）也可以在鼠细胞中诱导类似衰老的变化。
