Proteasome-dependent regulation of p21(WAF1/CIP1) expression
Proteasome-dependent regulation of p21(WAF1/CIP1) expression
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DOI：
10.1006/bbrc.1996.1546
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发表时间：
1996-10-14
影响因子：
3.1
通讯作者：
ElDeiry, WS
中科院分区：
文献类型：
--
作者：
Blagosklonny, MV;Wu, GS;ElDeiry, WS
调节蛋白的蛋白酶体依赖性降解是细胞周期控制的已知机制。我们发现，蛋白酶体特异性抑制剂lactacystin（LC）诱导表达的细胞周期抑制剂p21（WAF 1/CIP 1）在人类癌细胞中，无论其p53的状态。野生型（wt）p53和p21蛋白水平增加了两个小时的野生型p53含有细胞，而突变型（mt）p53水平下降，p21水平的增加被延迟到6小时后，蛋白水解抑制LC在me p53表达细胞。我们发现，野生型，但不是mt p53表达细胞增加p21 mRNA和p21启动子报告水平LC曝光后，表明转录诱导p21。放线菌酮对蛋白质合成的抑制作用表明，在含有突变型p53的细胞中，LC存在下p21蛋白半衰期增加。p21的诱导与LC的细胞抑制作用相关。结果表明，p21蛋白的表达可以增加转录机制，以及抑制蛋白水解LC。(C)出版社：Academic Press，Inc.
Proteasome-dependent degradation of regulatory proteins is a known mechanism of cell cycle control. We found that the proteasome-specific inhibitor lactacystin (LC) induced expression of the cell cycle inhibitor p21(WAF1/CIP1) in human cancer cells regardless of their p53 status. Both wild-type (wt) p53 and p21 protein levels increased by two hours in wt p53 containing cells, whereas mutant (mt) p53 levels decreased and the increase in p21 levels was delayed to 6 hr following inhibition of proteolysis by LC in me p53 expressing cells. We found that wt but not mt p53 expressing cells increased p21 mRNA and p21-promoter reporter levels following LC exposure, suggesting transcriptional induction of p21. Inhibition of protein synthesis by cycloheximide demonstrated increased p21 protein half-life in the presence of LC in mutant p53 containing cells. p21 induction was correlated with the cytostatic effects of LC. The results suggest that p21 protein expression could be increased by transcriptional mechanisms as well as inhibition of proteolysis by LC. (C) 1996 Academic Press, Inc.