Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice
Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice
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DOI：
10.1038/sj.onc.1203366
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发表时间：
2000-02-03
期刊：
影响因子：
8
通讯作者：
May, E
中科院分区：
文献类型：
--
作者：
Bouvard, V;Zaitchouk, T;May, E
P53肿瘤抑制蛋白在体内协调对遗传毒性应激的适应性反应的机制尚不清楚。P53被证明可以反式激活几个基因，这些基因可能参与两种主要的细胞反应，即生长停滞和细胞凋亡。为了进一步了解P53转录活性的组织特异性调控，我们进行了一项广泛的研究，观察了四个特征良好的P53反应基因在伽玛射线照射前后在P53野生型(P53+/+)和P53缺陷(P53-/-)小鼠中的表达。选择waf1、bax、fas和mdm2基因是因为它们在细胞对胁迫的反应中具有不同的潜在作用。我们的数据表明，照射组织中Bax、Fas和MDM2的mRNA上调严格依赖于P53，并证实了WAFL的这一发现。它们进一步强调了复杂水平的调控机制，这些机制可能导致在体内通过p53选择性地转录激活基因。此外，我们的结果还为P53参与这四个基因在某些器官中的基础mRNA表达提供了依据。最后，Bax和p21Waf-1蛋白的原位表达表明，至少在淋巴器官中，选择性的p53靶基因表达与细胞对电离辐射的特殊反应之间存在直接关联。
The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tissue-specific regulation of p53 transcriptional activity, we performed an extensive study looking at the expression of four well characterized p53-responsive genes, before and after gamma-irradiation in p53 wild-type (p53 +/+) and p53-deficient (p53 -/-) mice. The waf1, bax, fas and mdm2 genes were chosen for their different potential roles in the cellular response to stress. Our data demonstrate the strict p53-dependence of mRNA up-regulation for bax, fas and mdm2 in irradiated tissues and confirm such findings for wafl. They further highlight complex levels of regulatory mechanisms that could lead, in vivo, to selective transcriptional activation of genes by p53. In addition, our results provide arguments for the involvement of p53 in the basal mRNA expression of the four genes in some organs. Finally, in situ expression of Bax and p21Waf-1 protein suggests, at least in lymphoid organs, a direct correlation between selective p53-target gene expression and particular response of a cell to ionising radiation.