| First Author | Malek S | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 48 | Pages | 45225-35 |
| PubMed ID | 11571291 | Mgi Jnum | J:72969 |
| Mgi Id | MGI:2154058 | Doi | 10.1074/jbc.M105865200 |
| Citation | Malek S, et al. (2001) Ikappa Bbeta, but Not Ikappa Balpha, Functions as a Classical Cytoplasmic Inhibitor of NF-kappa B Dimers by Masking Both NF-kappa B Nuclear Localization Sequences in Resting Cells. J Biol Chem 276(48):45225-35 |
| abstractText | NF-kappaB dimers, inhibitor IkappaB proteins, and NF-kappaB.IkappaB complexes exhibit distinct patterns in partitioning between nuclear and cytoplasmic cellular compartments. IkappaB-dependent modulation of NF-kappaB subcellular localization represents one of the more poorly understood processes in the NF-kappaB signaling pathway. In this study, we have combined in vitro biochemical and cell-based methods to elucidate differences in NF-kappaB regulation exhibited by the inhibitors IkappaBbeta and IkappaBalpha. We show that although both IkappaBalpha and IkappaBbeta bind to NF-kappaB with similar global architecture and stability, significant differences exist that contribute to their unique functional roles. IkappaBbeta derives its high affinity toward NF-kappaB dimers by binding to both NF-kappaB subunit nuclear localization signals. In contrast, IkappaBalpha contacts only one NF-kappaB NLS and employs its carboxyl-terminal proline, glutamic acid, serine, and threonine-rich region for high affinity NF-kappaB binding. We show that the presence of one free NLS in the NF-kappaB.IkappaBalpha complex renders it a dynamic nucleocytoplasmic complex, whereas NF-kappaB.IkappaBbeta complexes are localized to the cytoplasm of resting cells. |
