Deregulated messenger RNA expression during T cell apoptosis.
Deregulated messenger RNA expression during T cell apoptosis.
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T 细胞凋亡过程中信使 RNA 表达失调。
DOI：
10.1093/nar/23.23.4857
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发表时间：
1995
影响因子：
14.9
通讯作者：
Ziff,EB
中科院分区：
文献类型：
--
作者：
Kerkhoff,E;Ziff,EB
依赖IL-2的小鼠细胞毒性T细胞系CTLL-2在失去其特定的细胞因子后会经历程序性细胞死亡。我们分析了IL-2剥夺后细胞周期相关基因的表达。在这里，我们表明，作为凋亡程序的一部分，mRNA水平的普遍下降和重新上升。去IL-2后1.5~3h，细胞周期功能相关基因如cyClinD2、cyClinD3、cyClinB1、c-myandmax等的表达水平下降。值得注意的是，在增殖、生长停滞和分化的细胞中表达的axmRNA，与其他mRNAs一样被下调。令人惊讶的是，在1.5-3h下降的mRNAs在10-14h再次上升，这一时间紧随第一次检测到凋亡DNA降解的时间，在8h，但通过台盼蓝排除法测量，在14h实际丧失了活性。在所有被分析的基因中，只有S阶段特异的组蛋白H4基因的表达抵抗了最初的减少，并在细胞死亡的过程中逐渐下降。对c-Myc蛋白合成的测量表明，在凋亡程序的后期，累积的重新诱导的mRNA没有翻译成蛋白质。由于转录调控被证明依赖于染色质结构，因此重新诱导可能是由于凋亡细胞染色质结构的改变导致染色质松弛而触发的。
The IL-2 dependent murine cytotoxic T cell line CTLL-2 undergoes programmed cell death when deprived of its specific cytokine. We analyzed the expression of cell cycle related genes after IL-2 deprivation. Here we show that a generalized decrease and re elevation of the levels of mRNA takes place as part of the apoptotic program. The levels of several mRNAs encoding cell cycle functions, including cyclinD2, cyclinD3, cyclinB1, c-mycandmaxall declined at 1.5–3 h following IL-2 deprivation. Notably, themaxmRNA, which was shown to be expressed in proliferating, growth arrested and differentiated cells, is down regulated with the same kinetics as the other mRNAs. Surprisingly, the mRNAs whose levels declined at 1.5–3 h rose again at 10–14 h, a time which closely followed the time of the first detection of apoptotic DNA degradation, at 8 h, but which proceeds actual loss of viability, at 14 h, as measured by trypan blue exclusion. Of all analyzed genes only the expression of the S-phase specific histoneH4gene resists the initial decrease and declines gradually over the course of cell death. Measurement of c-Myc protein synthesis at a late stage of the apoptotic program revealed that the accumulated reinduced mRNA is not translated into protein. Because transcriptional regulation has been shown to be dependent on the chromatin structure, the reinduction may be triggered by relaxation of the chromatin caused by alterations in the chromatin structure of apoptotic cells.