| First Author | Aguilera C | Year | 2006 |
| Journal | J Cell Sci | Volume | 119 |
| Issue | Pt 17 | Pages | 3695-704 |
| PubMed ID | 16931600 | Mgi Jnum | J:113130 |
| Mgi Id | MGI:3664531 | Doi | 10.1242/jcs.03086 |
| Citation | Aguilera C, et al. (2006) Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins. J Cell Sci 119(Pt 17):3695-704 |
| abstractText | IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling. |
