| First Author | Kensche T | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 28 | Pages | 23626-34 |
| PubMed ID | 22605335 | Mgi Jnum | J:192990 |
| Mgi Id | MGI:5467192 | Doi | 10.1074/jbc.M112.347195 |
| Citation | Kensche T, et al. (2012) Analysis of nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO) binding to linear and lysine-linked ubiquitin chains and its role in the activation of NF-kappaB. J Biol Chem 287(28):23626-34 |
| abstractText | Nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO), a component of the inhibitor of kappaB kinase (IKK) complex, controls NF-kappaB signaling by binding to ubiquitin chains. Structural studies of NEMO provided a rationale for the specific binding between the UBAN (ubiquitin binding in ABIN and NEMO) domain of NEMO and linear (Met-1-linked) di-ubiquitin chains. Full-length NEMO can also interact with Lys-11-, Lys-48-, and Lys-63-linked ubiquitin chains of varying length in cells. Here, we show that purified full-length NEMO binds preferentially to linear ubiquitin chains in competition with lysine-linked ubiquitin chains of defined length, including long Lys-63-linked deca-ubiquitins. Linear di-ubiquitins were sufficient to activate both the IKK complex in vitro and to trigger maximal NF-kappaB activation in cells. In TNFalpha-stimulated cells, NEMO chimeras engineered to bind exclusively to Lys-63-linked ubiquitin chains mediated partial NF-kappaB activation compared with cells expressing NEMO that binds to linear ubiquitin chains. We propose that NEMO functions as a high affinity receptor for linear ubiquitin chains and a low affinity receptor for long lysine-linked ubiquitin chains. This phenomenon could explain quantitatively distinct NF-kappaB activation patterns in response to numerous cell stimuli. |
