TRAF2 exerts its antiapoptotic effect by regulating the expression of Kruppel-like factor LKLF
TRAF2 exerts its antiapoptotic effect by regulating the expression of Kruppel-like factor LKLF
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DOI：
10.1128/mcb.23.16.5849-5856.2003
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发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Liu, ZG
中科院分区：
文献类型：
--
作者：
Lin, Y;Ryan, J;Liu, ZG
肿瘤坏死因子受体（TNFR）相关因子2（TRAF 2）是介导TNF信号传导的关键因子之一。TRAF 2的缺失使细胞对TNF诱导的凋亡更敏感。尽管已知TRAF 2是TNF诱导的JNK和NF-κ B活化所必需的，但TRAF 2空细胞（TRAF 2（-/-））对TNF诱导的凋亡的敏感性增加的潜在机制尚未完全理解。为了研究潜在的机制，我们通过使用微阵列技术检测TRAF 2（-/-）和野生型成纤维细胞之间的基因表达差异。我们发现在TRAF 2（-/-）细胞中表达显著降低的基因之一是肺Kruppel样因子（LKLF）。我们的研究结果表明，LKLF的表达需要TRAF 2，但不依赖于TNF信号。虽然TRAF 2似乎在转录水平上调节LKLF基因的表达，但TRAF 2本身并不作为转录因子发挥作用。我们的研究结果表明，TRAF 2通过丝裂原活化蛋白激酶p38途径调节LKLF表达。更重要的是，TRAF 2（-/-）细胞中LKLF的异位表达保护细胞免受TNF诱导的凋亡。这些结果揭示了TRAF 2功能的一个新方面：通过调节基因的表达，如LKLF，TRAF 2控制细胞对凋亡的敏感性。
Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is one of the key factors that mediate TNF signaling. The deletion of TRAF2 renders cells more sensitive to TNF-induced apoptosis. Although TRAF2 is known to be required for TNF-induced JNK and NF-kappaB activation, the underlying mechanism of the increased sensitivity of TRAF2 null cells (TRAF2(-/-)) to TNF-induced apoptosis is not fully understood. To study the underlying mechanism, we examined the difference in gene expression between TRAF2(-/-) and wild-type fibroblast cells by using microarray technology. We found that one of the genes whose expression was dramatically decreased in TRAF2(-/-) cells was the lung Kruppel-like factor (LKLF). Our results indicate that the expression of LKLF requires TRAF2 but is independent of TNF signaling. Although it appears that TRAF2 regulates the expression of the LKLF gene at the transcription level, TRAF2 does not function as a transcription factor itself. Our results suggest that TRAF2 regulates LKLF expression through the mitogen-activated protein kinase p38 pathway. More importantly, ectopic expression of LKLF in TRAF2(-/-) cells protected cells against TNF-induced apoptosis. These results reveal a novel aspect of TRAF2 function: by regulating the expression of genes, such as LKLF, TRAF2 controls cell sensitivity to apoptosis.