IκBα and IκBα/NF-κB complexes are retained in the cytoplasm through interaction with a novel partner, RasGAP SH3-binding protein 2
IκBα and IκBα/NF-κB complexes are retained in the cytoplasm through interaction with a novel partner, RasGAP SH3-binding protein 2
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DOI：
10.1074/jbc.m004751200
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发表时间：
2000-11-17
影响因子：
4.8
通讯作者：
Dargemont, C
中科院分区：
文献类型：
--
作者：
Prigent, M;Barlat, I;Dargemont, C
I-kappaBα通过阻止核转录因子-kappaB在胞浆和细胞核内的转录活性，使核转录因子-kappaB从DNA中解离并转运回细胞质，非活性的NF-kappaB/I kappaBα复合体的细胞质定位受核转录因子-kappaB p65和I kappaBα核输入序列和活性CRM1介导的核输出相互掩蔽的控制。在这里，我们描述了解释I kappaBα或NF-kappaB/I kappaBα复合体细胞质锚定的另一种机制。I kappaBα的N末端结构域含有一个序列，负责I kappaBα的细胞质滞留，该序列由G3BP2特异性识别，G3BP2是一种细胞质蛋白，与IkBα和I kappaBα/NF-kappaB复合体相互作用。G3BP2由一个与NTF2蛋白同源的N末端结构域、一个足以与I kappaBα细胞质保留序列相互作用的酸性结构域、一个包含5个PXXP基序的区域和一个包含RNA结合基序的C末端结构域组成。G3BP2的过表达直接促进了I kappaBα在细胞质中的滞留，表明I kappaBα和NF-kappaB/I kappaBα复合体的亚细胞分布可能是核输入、核输出和细胞质保留之间的平衡的结果。G3BP2的分子组成表明，这个可能的支架蛋白可能将核转录因子-kappaB信号转导级联与核运输或RNA代谢等细胞功能联系起来。
I kappaB alpha inhibits the transcriptional activity of NF-kappaB both in the cytoplasm by preventing the nuclear translocation of NF-kappaB and in the nucleus where it dissociates NF-kappaB from DNA and transports it back to the cytoplasm, Cytoplasmic localization of inactive NF-kappaB/I kappaB alpha complexes is controlled by mutual masking of nuclear import sequences of NF-kappaB p65 and I kappaB alpha and active CRM1-mediated nuclear export. Here, we describe an additional mechanism accounting for the cytoplasmic anchoring of I kappaB alpha or NF-kappaB/I kappaB alpha complexes. The N-terminal domain of I kappaB alpha contains a sequence responsible for the cytoplasmic retention of I kappaB alpha that is specifically recognized by G3BP2, a cytoplasmic protein that interacts with both IKB alpha and I kappaB alpha /NF-kappaB complexes. G3BP2 is composed of an N-terminal domain homologous to the NTF2 protein, followed by an acidic domain sufficient for the interaction with the I kappaB alpha cytoplasmic retention sequence, a region containing five PXXP motifs and a C-terminal domain containing RNA-binding motifs. Overexpression of G3BP2 directly promotes retention of I kappaB alpha in the cytoplasm, indicating that subcellular distribution of I kappaB alpha and NF-kappaB/I kappaB alpha complexes likely results from a equilibrium between nuclear import, nuclear export, and cytoplasmic retention. The molecular organization of G3BP2 suggests that this putative scaffold protein might connect the NF-kappaB signal transduction cascade with cellular functions such as nuclear transport or RNA metabolism.