| First Author | Tao Z | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 45 | Pages | 15946-51 |
| PubMed ID | 25349408 | Mgi Jnum | J:216653 |
| Mgi Id | MGI:5609183 | Doi | 10.1073/pnas.1408552111 |
| Citation | Tao Z, et al. (2014) p100/IkappaBdelta sequesters and inhibits NF-kappaB through kappaBsome formation. Proc Natl Acad Sci U S A 111(45):15946-51 |
| abstractText | Degradation of I kappaB (kappaB) inhibitors is critical to activation of dimeric transcription factors of the NF-kappaB family. There are two types of IkappaB inhibitors: the prototypical IkappaBs (IkappaBalpha, IkappaBbeta, and IkappaBepsilon), which form low-molecular-weight (MW) IkappaB:NF-kappaB complexes that are highly stable, and the precursor IkappaBs (p105/IkappaBgamma and p100/IkappaBdelta), which form high-MW assemblies, thereby suppressing the activity of nearly half the cellular NF-kappaB [Savinova OV, Hoffmann A, Ghosh G (2009) Mol Cell 34(5):591-602]. The identity of these larger assemblies and their distinct roles in NF-kappaB inhibition are unknown. Using the X-ray crystal structure of the C-terminal domain of p100/IkappaBdelta and functional analysis of structure-guided mutants, we show that p100/IkappaBdelta forms high-MW (IkappaBdelta)4:(NF-kappaB)4 complexes, referred to as kappaBsomes. These IkappaBdelta-centric "kappaBsomes" are distinct from the 2:2 complexes formed by IkappaBgamma. The stability of the IkappaBdelta tetramer is enhanced upon association with NF-kappaB, and hence the high-MW assembly is essential for NF-kappaB inhibition. Furthermore, weakening of the IkappaBdelta tetramer impairs both its association with NF-kappaB subunits and stimulus-dependent processing into p52. The unique ability of p100/IkappaBdelta to stably interact with all NF-kappaB subunits by forming kappaBsomes demonstrates its importance in sequestering NF-kappaB subunits and releasing them as dictated by specific stimuli for developmental programs. |
