Herbig Utz, Sedivy John M
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 70 Ship Street, Box G-E438, Providence, RI 02903, USA.
Mech Ageing Dev. 2006 Jan;127(1):16-24. doi: 10.1016/j.mad.2005.09.002. Epub 2005 Oct 17.
After a limited number of divisions, most eukaryotic cells grown in culture will undergo a terminal growth arrest called cellular senescence. This growth arrest is thought to be a consequence of progressive telomere shortening that occurs due to incomplete DNA replication of the chromosome ends. In addition, cellular senescence can also be induced by a number of environmental stresses and signaling imbalances which are independent of telomere shortening. The cyclin dependent kinase inhibitors p21 and p16(INK4a) have been shown to execute and maintain the cell cycle arrest in senescence but the nature of the signals that cause upregulation of these inhibitors in senescent cells are only now starting to be discovered. Here we will review the current literature that leads us to propose a model how independent signals activate distinct signaling pathways to regulate p21 and p16(INK4a) levels in senescent cells.
在经历有限次数的分裂后，大多数在培养中生长的真核细胞会进入一种称为细胞衰老的终末生长停滞状态。这种生长停滞被认为是由于染色体末端DNA复制不完全导致端粒逐渐缩短的结果。此外，细胞衰老也可由多种与端粒缩短无关的环境应激和信号失衡诱导。细胞周期蛋白依赖性激酶抑制剂p21和p16(INK4a)已被证明可执行并维持衰老细胞中的细胞周期停滞，但导致这些抑制剂在衰老细胞中上调的信号的本质直到现在才开始被发现。在这里，我们将回顾当前的文献，这些文献使我们提出一个模型，即独立信号如何激活不同的信号通路来调节衰老细胞中p21和p16(INK4a)的水平。
