Tee A R, Proud C G
School of Life Sciences, Medical Sciences Institute/Wellcome Trust Building Complex, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
Cell Death Differ. 2001 Aug;8(8):841-9. doi: 10.1038/sj.cdd.4400876.
Treatment of Swiss 3T3 cells with staurosporine resulted in dephosphorylation of two proteins which play key roles in regulating mRNA translation. This occurred before the execution of apoptosis, assessed by caspase-3 activity. These translation regulators are p70 S6 kinase, which phosphorylates ribosomal protein S6, and eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1), which both lie downstream of the mammalian target of rapamycin (mTOR). This resulted in decreased p70 S6 kinase activity, dephosphorylation of ribosomal protein S6, increased binding of 4E-BP1 to eIF4E and a concomitant decrease in eIF4F complexes. Our data show that staurosporine impairs mTOR signalling in vivo but that this not due to direct inhibition of mTOR or to inhibition of protein kinase C. It is becoming clear that agents which cause apoptosis inactivate mTOR signalling as a common early response prior to the execution of apoptosis, i.e., before caspase activation.
用星形孢菌素处理瑞士3T3细胞会导致两种在调节mRNA翻译中起关键作用的蛋白质去磷酸化。这发生在通过半胱天冬酶-3活性评估的细胞凋亡执行之前。这些翻译调节因子是磷酸化核糖体蛋白S6的p70 S6激酶和真核起始因子（eIF）4E结合蛋白1（4E-BP1），它们都位于雷帕霉素哺乳动物靶标（mTOR）的下游。这导致p70 S6激酶活性降低、核糖体蛋白S6去磷酸化、4E-BP1与eIF4E的结合增加以及eIF4F复合物随之减少。我们的数据表明，星形孢菌素在体内损害mTOR信号传导，但这并非由于直接抑制mTOR或抑制蛋白激酶C。越来越清楚的是，导致细胞凋亡的药物会使mTOR信号传导失活，这是细胞凋亡执行之前（即半胱天冬酶激活之前）常见的早期反应。
