Adapter protein NRBP associates with Jab1 and negatively regulates AP-1 activity

Adapter protein NRBP associates with Jab1 and negatively regulates AP-1 activity
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DOI:
10.1016/j.febslet.2006.10.002
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发表时间:
2006-10-30
期刊:
影响因子:
3.5
通讯作者:
Wu, Jun
Wu, Jun
中科院分区:
生物学3区
文献类型:
--
作者:
Wang, Hui;Sun, Xiaoqing;Wu, Jun

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Jun激活结构域结合蛋白1(Jab 1)是激活蛋白-1(AP-1)的共激活因子,是COP 9信号体复合物的第五组分。它与多种蛋白质相互作用,并在多种信号通路和细胞功能(包括肿瘤发生)中发挥重要作用。我们发现Jab 1在体内与核受体结合蛋白(NRBP)相互作用,NRBP是一种进化上保守的具有激酶样结构域的衔接蛋白。我们进一步表明,NRBP抑制Jab 1诱导的c-Jun磷酸化和AP-1激活。最后,NRBP在哺乳动物细胞中的过表达特异性地抑制各种刺激引起的AP-1活化。总之,我们的数据表明,NRBP可能是Jab 1介导的功能,如基因转录和肿瘤进展的一个重要的负调节因子。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
Jun activation domain-binding protein 1 (Jab1) is a coactivator of activating protein-1 (AP-1) and is the fifth component of the COP9 signalosome complex. It interacts with a variety of proteins and plays important roles in diverse signaling pathways and cellular function including oncogenesis. We show here that Jab1 interacts in vivo with nuclear receptor binding protein (NRBP), an evolutionarily conserved adapter protein with a kinase-like domain. We further show that NRBP inhibits Jab1-induced phosphorylation of c-Jun and AP-1 activation. Finally, overexpression of NRBP in mammalian cells specifically inhibits AP-1 activation by various stimuli. Taken together, our data suggest that NRBP may be an important negative regulator of Jab1-mediated functions such as gene transcription and tumor progression. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.