共 33 条
p53-dependent cell cycle arrest induced by N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal in platelet-derived growth factor-stimulated human fibroblasts
被引:68
作者:
Dietrich, C
[1
]
Bartsch, T
[1
]
Schanz, F
[1
]
Oesch, F
[1
]
Wieser, RJ
[1
]
机构:
[1] UNIV MAINZ,INST TOXICOL,D-55131 MAINZ,GERMANY
来源:
关键词:
D O I:
10.1073/pnas.93.20.10815
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Proteases are known to play important roles in cell growth control, although the underlying mechanisms are still poorly understood, Here we show that the protease inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal induced cell cycle arrest in platelet-derived growth factor-stimulated human fibroblasts at the G(1)/S boundary of the cell cycle by inhibiting the proteasome, Inhibition of the proteasome resulted in accumulation of the tumor suppressor p53, which was followed by an increase in the amount of the cyclin-dependent kinase-inhibitor p21, As a consequence, both phosphorylation and activity of the cyclin-dependent kinase 2/cyclin E complex were inhibited, We further observed that the retinoblastoma gene product, pRb, remained in the hypophosphorylated state, thus preventing cells from progression into the S-phase, These studies strongly support the hypothesis that the proteasome is a key regulator in the G(1)-phase of cell cycle progression.
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页码:10815 / 10819
页数:5
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