Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-κB
Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-κB
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DOI：
10.1016/j.bbrc.2008.06.128
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发表时间：
2008-09-26
影响因子：
3.1
通讯作者：
Swart, Guido W. M.
中科院分区：
文献类型：
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作者：
Takahashi, Nozomi;van Kilsdonk, Jeroen W. J.;Swart, Guido W. M.
核孔蛋白 88 kDa (Nup88) 是一种肿瘤标志物，在多种类型的癌症中过度表达。据报道，在果蝇中，Nup88 (mbo) 选择性介导 NF-κ B 的核细胞质转运，NF-κ B 是一种参与免疫反应、细胞凋亡和癌症的普遍存在的转录因子。我们研究了 Nup88 在哺乳动物细胞中的功能。通过小干扰 RNA (siRNA) 选择性耗尽 Nup88 可抑制 NF-kappa B 依赖性报告基因激活和 NF-kappa B 核转位，而不影响 NIH3T3 细胞中的上游激活途径。相反，糖皮质激素受体的核易位并未因Nup88的耗尽而减少。在过度表达 NUP88 的转移性黑色素瘤细胞中，在细胞核和细胞质中均发现 NF-κ B 的组成型激活。这些细胞中 Nup88 的缺失减少了 TNF 诱导的 NF-κ B 亚基的核积累。我们得出结论，Nup88 在核细胞质转运水平上调节 NF-κ B 的活性。因此，肿瘤细胞中 Nup88 的过度表达可能参与组成型 NF-κ B 激活。 (C) 2008 Elsevier Inc. 保留所有权利。
Nucleoporin 88 kDa (Nup88) is a tumor marker, overexpressed in various types of cancer. In Drosophila Nup88 (mbo) was reported to selectively mediate the nucleocytoplasmic transport of NF-kappa B, an Ubiquitous transcription factor involved in immune responses, apoptosis, and cancer. We addressed the function of Nup88 in mammalian cells. Selective depletion of Nup88 by small interfering RNA (siRNA) inhibited NF-kappa B-dependent reporter gene activation and the nuclear translocation of NF-kappa B without affecting the Upstream activation pathway in NIH3T3 cells. In contrast, nuclear translocation of glucocorticoid receptor was not reduced by the depletion of Nup88. In metastatic melanoma cells overexpressing NUP88, constitutive activation of NF-kappa B was found both in nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear accumulation of NF-kappa B subunits. We conclude that Nup88 regulates the activity of NF-kappa B at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-kappa B activation. (C) 2008 Elsevier Inc. All rights reserved.