| First Author | Vig E | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 11 | Pages | 7859-66 |
| PubMed ID | 11096118 | Mgi Jnum | J:67984 |
| Mgi Id | MGI:1931897 | Doi | 10.1074/jbc.M010399200 |
| Citation | Vig E, et al. (2001) SIMPL is a tumor necrosis factor-specific regulator of nuclear factor-kappaB activity. J Biol Chem 276(11):7859-66 |
| abstractText | The IL-1 receptor-associated kinase (IRAK/mPLK) is linked to the regulation of nuclear factor-kappaB (NF-kappaB)-dependent gene expression. Here we describe a novel binding partner of IRAK/mPLK that we term SIMPL (signaling molecule that associates with the mouse pelle-like kinase). Overexpression of SIMPL leads to the activation of NF-kappaB-dependent promoters, and inactivation of SIMPL inhibits IRAK/mPLK as well as tumor necrosis factor receptor type I-induced NF-kappaB activity. Dominant inhibitory alleles of IkappaB kinase (IKKalpha or IKKbeta) block the activation of NF-kappaB by IRAK/mPLK and SIMPL. Furthermore, SIMPL binds IRAK/mPLK and the IKKs in vitro and in vivo. In the presence of antisense mRNA to SIMPL, the physical association between IRAK/mPLK and IKKbeta but not IRAK/mPLK and IKKalpha is greatly diminished. Moreover, dominant-negative SIMPL blocks IKKalpha- or IKKbeta-induced NF-kappaB activity. These results lead us to propose a model in which SIMPL functions to regulate NF-kappaB activity by linking IRAK/mPLK to IKKbeta/alpha-containing complexes. |
