| First Author | Yong Y | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 14 | Pages | 2802-16 |
| PubMed ID | 21606193 | Mgi Jnum | J:174079 |
| Mgi Id | MGI:5051865 | Doi | 10.1128/MCB.00253-10 |
| Citation | Yong Y, et al. (2011) Exogenous Signal-Independent Nuclear I{kappa}B Kinase Activation Triggered by Nkx3.2 Enables Constitutive Nuclear Degradation of I{kappa}B-{alpha} in Chondrocytes. Mol Cell Biol 31(14):2802-16 |
| abstractText | NF-kappaB is a multifunctional transcription factor involved in diverse biological processes. It has been well documented that NF-kappaB can be activated in response to various stimuli. While signal-inducible NF-kappaB activation mechanisms have been extensively characterized, exogenous signal-independent intrinsic NF-kappaB activation processes remain poorly understood. Here we show that IkappaB kinase beta (IKKbeta) can be intrinsically activated in the nucleus by a homeobox protein termed Nkx3.2 in the absence of exogenous IKK-activating signals. We found that ubiquitin chain-dependent, but persistent, interactions between Nkx3.2 and NEMO (also known as IKKgamma) can give rise to constitutive IKKbeta activation in the nucleus. Once the Nkx3.2-NEMO-IKKbeta complex is formed in the nucleus, IKKbeta-induced Nkx3.2 phosphorylation at Ser148 and Ser168 allows betaTrCP to be engaged to cause IkappaB-alpha ubiquitination independent of IkappaB-alpha phosphorylation at Ser32 and Ser36. Taken together, our results provide a novel molecular explanation as to how an intracellular factor such as Nkx3.2 can accomplish persistent nuclear IKK activation to enable intrinsic and constitutive degradation of IkappaB in the nucleus in the absence of exogenous NF-kappaB-activating signals, which, in turn, plays a role in chondrocyte viability maintenance. |
