p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells
p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells
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DOI：
10.1038/sj.cdd.4400801
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发表时间：
2001-03-01
影响因子：
12.4
通讯作者：
Watson, CJ
中科院分区：
文献类型：
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作者：
MacLaren, AP;Chapman, RS;Watson, CJ
我们在小鼠乳腺细胞系KIM-2细胞中使用肽醛抑制剂MG132检测了26S蛋白酶体的抑制效果，这些研究表明蛋白酶体在细胞活力中具有明确的功能要求。在MG132处理后，KIM-2细胞中观察到凋亡的诱导，这种死亡被证明依赖于细胞积极地穿越细胞周期。KIM-2细胞是用温度敏感t抗原（Tag）生成的，在允许温度（33℃）下的研究表明，Tag结合蛋白对这种凋亡反应是必不可少的。对另外两种细胞系HC11（一种携带突变p53等位基因的乳腺上皮细胞系）和p53无基因ES细胞的研究表明，p53在蛋白酶体抑制诱导的凋亡中是积极需要的。这些结果表明26S蛋白酶体降解途径在增殖细胞的细胞周期过程中起着关键作用。
We have examined the effects of inhibition of the 26S proteasome in a murine mammary cell line, KIM-2 cells using the peptide aldehyde inhibitor MG132, These studies have demonstrated a clear requirement for proteasome function in cell viability. Induction of apoptosis was observed following MG132 treatment in KIM-2 cells and this death was shown to be dependent on the cell actively traversing the cell cycle. KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 C) have shown that a Tag binding protein was essential for this apoptotic response, Studies in two additional cell lines, HC11, which is a mammary epithelial cell line carrying mutant p53 alleles and p53 null ES cells suggest that p53 is actively required for the apoptosis induced as a consequence of proteasome inhibition, These results suggest a pivotal role for the 26S proteasome degradation pathway in progression through the cell cycle in proliferating cells.