NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway.
NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway.
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DOI：
10.1038/onc.2015.95
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发表时间：
2016-01-21
期刊：
影响因子：
8
通讯作者：
Baek SJ
中科院分区：
文献类型：
--
作者：
Min KW;Liggett JL;Silva G;Wu WW;Wang R;Shen RF;Eling TE;Baek SJ
蛋白质动力学、修饰和运输都是可以调节蛋白质活性的过程。越来越多的证据有力地表明，许多蛋白质发挥独特的作用依赖于细胞的位置。非甾体抗炎药激活基因-1（NAG-1）是一种TGF-β超家族蛋白，在癌症、肥胖和炎症中发挥作用。NAG-1被合成并切割成成熟肽，其最终分泌到细胞外基质（ECM）中。在这项研究中，我们发现全长NAG-1不仅在细胞质和ECM中表达，而且在细胞核中表达。NAG-1动态地移动到细胞核，输出到细胞质中，并进一步转运到ECM中。我们还发现，核NAG-1有助于通过中断Smad复合物抑制Smad通路。总的来说，我们的研究表明，NAG-1定位于细胞核，并提供了新的证据，NAG-1控制转录调控Smad途径。
Protein dynamics, modifications, and trafficking are all processes that can modulate protein activity. Accumulating evidence strongly suggests that many proteins play distinctive roles dependent on cellular location. Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) is a TGF-β superfamily protein that plays a role in cancer, obesity, and inflammation. NAG-1 is synthesized and cleaved into a mature peptide, which is ultimately secreted into the extracellular matrix (ECM). In this study, we have found that full-length NAG-1 is expressed in not only the cytoplasm and ECM, but also in the nucleus. NAG-1 is dynamically moved to the nucleus, exported into cytoplasm, and further transported into the ECM. We have also found that nuclear NAG-1 contributes to inhibition of the Smad pathway by interrupting the Smad complex. Overall, our study indicates that NAG-1 is localized in the nucleus and provides new evidence that NAG-1 controls transcriptional regulation in the Smad pathway.