RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY
RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY
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DOI：
10.1038/377552a0
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发表时间：
1995-10-12
期刊：
影响因子：
64.8
通讯作者：
HANNON, GJ
中科院分区：
文献类型：
--
作者：
BRUGAROLAS, J;CHANDRASEKARAN, C;HANNON, GJ
蛋白p21是细胞周期蛋白依赖性激酶（1 - 3）和增殖细胞核抗原（PCNA）（4）的双重抑制剂，这两者都是细胞周期进程所必需的。p21基因受p53的转录调控（参考文献5），这表明p21可能促进p53依赖性细胞周期阻滞或细胞凋亡。p21还与细胞衰老（6）以及终末分化时的细胞周期退出（7 - 9）有关。在此，我们利用部分由p21（-/-）细胞和部分由p21（+/+）细胞组成的嵌合小鼠来研究p21在这些过程中的作用。对成年小肠的p21（+/+）和p21（-/-）成分进行的免疫组织化学研究表明，p21的缺失对四种主要肠道上皮细胞谱系的迁移相关分化或辐射后p53依赖性细胞凋亡没有可检测到的影响。然而，p21（-/-）小鼠胚胎成纤维细胞在DNA损伤后经历G1期阻滞的能力受损。
THE protein p21 is a dual inhibitor of cyclin-dependent kinases(1-3) and proliferating-cell nuclear antigen (PCNA)(4), both of which are required for passage through the cell cycle. The p21 gene is under the transcriptional control of p53 (ref. 5), suggesting that p21 might promote p53-dependent cell cycle arrest or apoptosis. p21 has also been implicated in cell senescence(6) and in cell-cycle withdrawal upon termination differentiation(7-9). Here we investigate the role of p21 in these processes using chimaeric mice composed partly of p21(-/-) and partly of p21(+/+) cells. Immunohistochemical studies of the p21(+/+) and p21(-/-) components of adult small intestine indicated that deletion of p21 had no detectable effect on the migration-associated differentiation of the four principal intestinal epithelial cell lineages or on p53-dependent apoptosis following irradiation. However, p21(-/-) mouse embryo fibroblasts are impaired in their ability to undergo G1 arrest following DNA damage.