Role of p53 in cell cycle regulation and apoptosis following exposure to proteasome inhibitors.
Role of p53 in cell cycle regulation and apoptosis following exposure to proteasome inhibitors.
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发表时间：
2000-05
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通讯作者：
F. Chen;Daniel T. Chang;M. Goh;S. Klibanov;M. Ljungman
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作者：
F. Chen;Daniel T. Chang;M. Goh;S. Klibanov;M. Ljungman
在这项研究中，我们探讨了26 S蛋白酶体的抑制剂对细胞周期分布和诱导细胞凋亡的人皮肤成纤维细胞和结肠癌细胞在其p53状态不同的影响。我们发现蛋白酶体抑制导致p53的核积累。这是令人惊讶的，因为人们认为p53的降解是由细胞质26 S蛋白酶体介导的。p53的核积聚伴随着p21 WAF 1 mRNA和蛋白的诱导以及进入S期的细胞减少。有趣的是，具有受损的p53功能的细胞显示出细胞周期的G2-M期的细胞比例显著增加，并且蛋白酶体抑制后细胞凋亡的诱导减弱。两者合计，我们的研究结果表明，蛋白酶体抑制的结果在核积累的p53和p53刺激诱导G1期阻滞和细胞凋亡。
In this study, we explored what effect inhibitors of the 26S proteasome have on cell cycle distribution and induction of apoptosis in human skin fibroblasts and colon cancer cells differing in their p53 status. We found that proteasome inhibition resulted in nuclear accumulation of p53. This was surprising because it is thought that the degradation of p53 is mediated by cytoplasmic 26S proteasomes. Nuclear accumulation of p53 was accompanied by the induction of both p21WAF1 mRNA and protein as well as a decrease in cells entering S phase. Interestingly, cells with compromised p53 function showed a marked increase in the proportion of cells in the G2-M phase of the cell cycle and an attenuated induction of apoptosis after proteasome inhibition. Taken together, our results suggest that proteasome inhibition results in nuclear accumulation of p53 and a p53-stimulated induction of both G1 arrest and apoptosis.