Sun Shaogang, Tang Yujie, Lou Xiwen, Zhu Lianhui, Yang Kai, Zhang Bianhong, Shi Hexin, Wang Chen
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J Cell Biol. 2007 Jul 16;178(2):231-44. doi: 10.1083/jcb.200611081. Epub 2007 Jul 9.
As a latent transcription factor, nuclear factor kappaB (NF-kappaB) translocates from the cytoplasm into the nucleus upon stimulation and mediates the expression of genes that are important in immunity, inflammation, and development. However, little is known about how it is regulated inside the nucleus. By a two-hybrid approach, we identify a prefoldin-like protein, ubiquitously expressed transcript (UXT), that is expressed predominantly and interacts specifically with NF-kappaB inside the nucleus. RNA interference knockdown of UXT leads to impaired NF-kappaB activity and dramatically attenuates the expression of NF-kappaB-dependent genes. This interference also sensitizes cells to apoptosis by tumor necrosis factor-alpha. Furthermore, UXT forms a dynamic complex with NF-kappaB and is recruited to the NF-kappaB enhanceosome upon stimulation. Interestingly, the UXT protein level correlates with constitutive NF-kappaB activity in human prostate cancer cell lines. The presence of NF-kappaB within the nucleus of stimulated or constitutively active cells is considerably diminished with decreased endogenous UXT levels. Our results reveal that UXT is an integral component of the NF-kappaB enhanceosome and is essential for its nuclear function, which uncovers a new mechanism of NF-kappaB regulation.
作为一种潜在的转录因子，核因子κB（NF-κB）在受到刺激时从细胞质转位至细胞核，并介导在免疫、炎症和发育过程中起重要作用的基因的表达。然而，关于其在细胞核内如何被调控却知之甚少。通过双杂交方法，我们鉴定出一种遍在表达转录本（UXT），它是一种类前折叠蛋白，在细胞核内主要表达且与NF-κB特异性相互作用。RNA干扰敲低UXT会导致NF-κB活性受损，并显著减弱NF-κB依赖性基因的表达。这种干扰还会使细胞对肿瘤坏死因子-α诱导的凋亡敏感。此外，UXT与NF-κB形成动态复合物，并在受到刺激时被招募至NF-κB增强体。有趣的是，在人前列腺癌细胞系中，UXT蛋白水平与组成型NF-κB活性相关。随着内源性UXT水平降低，受刺激或组成型激活细胞细胞核内NF-κB的含量会大幅减少。我们的结果表明，UXT是NF-κB增强体的一个组成部分，对其核功能至关重要，这揭示了一种新的NF-κB调控机制。
