Department of Molecular Medicine, and Max Planck Research Group on Stem Cell Aging, University of Ulm, Ulm, Germany.
EMBO Rep. 2010 Aug;11(8):619-25. doi: 10.1038/embor.2010.83. Epub 2010 Jun 25.
Telomere shortening limits the proliferation of primary human fibroblasts by the induction of senescence, which is mediated by ataxia telangiectasia mutated-dependent activation of p53. Here, we show that CHK2 deletion impairs the induction of senescence in mouse and human fibroblasts. By contrast, CHK2 deletion did not improve the stem-cell function, organ maintenance and lifespan of telomere dysfunctional mice and did not prevent the induction of p53/p21, apoptosis and cell-cycle arrest in telomere dysfunctional progenitor cells. Together, these results indicate that CHK2 mediates the induction of senescence in fibroblasts, but is dispensable for the induction of telomere dysfunction checkpoints at the stem and progenitor cell level in vivo.
端粒缩短通过诱导衰老限制原代人成纤维细胞的增殖，这种衰老由共济失调毛细血管扩张突变依赖的 p53 激活所介导。在这里，我们表明 CHK2 缺失会损害小鼠和人成纤维细胞中衰老的诱导。相比之下，CHK2 缺失并没有改善端粒功能障碍小鼠的干细胞功能、器官维持和寿命，也不能防止端粒功能障碍祖细胞中 p53/p21 的诱导、细胞凋亡和细胞周期停滞。总之，这些结果表明 CHK2 介导成纤维细胞中衰老的诱导，但在体内干细胞和祖细胞水平上，CHK2 对于端粒功能障碍检查点的诱导是可有可无的。
