IkappaBalpha and IkappaBalpha /NF-kappa B complexes are retained in the cytoplasm through interaction with a novel partner, RasGAP SH3-binding protein 2
| Autor: | M, Prigent, I, Barlat, H, Langen, C, Dargemont |
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| Rok vydání: | 2000 |
| Předmět: |
Cytoplasm
Macromolecular Substances Recombinant Fusion Proteins Nuclear Localization Signals Pyruvate Kinase Fluorescent Antibody Technique Protein Sorting Signals Transfection Receptors Glucocorticoid NF-KappaB Inhibitor alpha Genes Reporter Humans Poly-ADP-Ribose Binding Proteins Adaptor Proteins Signal Transducing Binding Sites DNA Helicases NF-kappa B RNA-Binding Proteins Precipitin Tests Protein Structure Tertiary DNA-Binding Proteins Repressor Proteins Protein Transport RNA Recognition Motif Proteins Mutation I-kappa B Proteins Carrier Proteins RNA Helicases HeLa Cells Protein Binding |
| Zdroj: | The Journal of biological chemistry. 275(46) |
| ISSN: | 0021-9258 |
| Popis: | IkappaBalpha 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/IkappaBalpha complexes is controlled by mutual masking of nuclear import sequences of NF-kappaB p65 and IkappaBalpha and active CRM1-mediated nuclear export. Here, we describe an additional mechanism accounting for the cytoplasmic anchoring of IkappaBalpha or NF-kappaB/IkappaBalpha complexes. The N-terminal domain of IkappaBalpha contains a sequence responsible for the cytoplasmic retention of IkappaBalpha that is specifically recognized by G3BP2, a cytoplasmic protein that interacts with both IkappaBalpha and IkappaBalpha/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 IkappaBalpha 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 IkappaBalpha in the cytoplasm, indicating that subcellular distribution of IkappaBalpha and NF-kappaB/IkappaBalpha 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. |
| Databáze: | OpenAIRE |
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