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首页> 外文期刊>Molecular Cancer >Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells
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Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells

机译：p38和JNK MAPK信号通路以及抑癌p53在A549肺癌细胞中诱导Ad-eIF5A1诱导凋亡的作用

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Background The eukaryotic translation initiation factor 5A1 (eIF5A1) is a highly conserved protein involved in many cellular processes including cell division, translation, apoptosis, and inflammation. Induction of apoptosis is the only function of eIF5A1 that is known to be independent of post-translational hypusine modification. In the present study, we investigated the involvement of mitogen- and stress-activated protein kinases during apoptosis of A549 lung cancer cells infected with adenovirus expressing eIF5A1 or a mutant of eIF5A1 that cannot be hypusinated (eIF5A1K50A). Methods Using adenoviral-mediated transfection of human A549 lung cancer cells to over-express eIF5A1 and eIF5A1K50A, the mechanism by which unhypusinated eIF5A1 induces apoptosis was investigated by Western blotting, flow cytometry, and use of MAPK and p53 inhibitors. Results Phosphorylation of ERK, p38 MAPK , and JNK was observed in response to adenovirus-mediated over-expression of eIF5A1 or eIF5A1K50A, along with phosphorylation and stabilization of the p53 tumor suppressor protein. Synthetic inhibitors of p38 and JNK kinase activity, but not inhibitors of ERK1/2 or p53 activity, significantly inhibited apoptosis induced by Ad-eIF5A1. Importantly, normal lung cells were more resistant to apoptosis induced by eIF5A1 and eIF5A1K50A than A549 lung cancer cells. Conclusions Collectively these data indicate that p38 and JNK MAP kinase signaling are important for eIF5A1-induced cell death and that induction of apoptosis was not dependent on p53 activity.
机译：背景真核翻译起始因子5A1（eIF5A1）是高度保守的蛋白质，参与许多细胞过程，包括细胞分裂，翻译，凋亡和炎症。凋亡的诱导是eIF5A1的唯一功能，已知它独立于翻译后的hysupsine修饰。在本研究中，我们研究了腺病毒感染表达eIF5A1或不能被羟化的eIF5A1突变体的腺病毒感染的A549肺癌细胞凋亡过程中，促分裂原和应激激活蛋白激酶的参与（eIF5A1 K50A ）。方法以腺病毒为载体转染人A549肺癌细胞，以过量表达eIF5A1和eIF5A1 K50A ，通过蛋白印迹法研究未加血嘧啶的eIF5A1诱导细胞凋亡的机制。 ，流式细胞仪以及MAPK和p53抑制剂的使用。结果在腺病毒介导的eIF5A1或eIF5A1 K50A 的过表达中，观察到ERK，p38 MAPK和JNK的磷酸化，以及ERK，p38 MAPK和JNK的磷酸化和稳定。 p53肿瘤抑制蛋白。 p38和JNK激酶活性的合成抑制剂，而不是ERK1 / 2或p53活性的抑制剂，显着抑制Ad-eIF5A1诱导的细胞凋亡。重要的是，正常的肺癌细胞对eIF5A1和eIF5A1 class="a-plus-plus"> K50A 诱导的凋亡的耐受性要高于A549肺癌细胞。结论总而言之，这些数据表明p38和JNK MAP激酶信号转导对于eIF5A1诱导的细胞死亡很重要，并且凋亡的诱导并不依赖于p53活性。

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