| First Author | Chew J | Year | 2009 |
| Journal | Nat Cell Biol | Volume | 11 |
| Issue | 5 | Pages | 659-66 |
| PubMed ID | 19377466 | Mgi Jnum | J:155072 |
| Mgi Id | MGI:4412225 | Doi | 10.1038/ncb1873 |
| Citation | Chew J, et al. (2009) WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol 11(5):659-66 |
| abstractText | Post-translational modifications of NF-kappaB through phosphorylations enhance its transactivation potential. Much is known about the kinases that phosphorylate NF-kappaB, but little is known about the phosphatases that dephosphorylate it. By using a genome-scale siRNA screen, we identified the WIP1 phosphatase as a negative regulator of NF-kappaB signalling. WIP1-mediated regulation of NF-kappaB occurs in both a p38-dependent and independent manner. Overexpression of WIP1 resulted in decreased NF-kappaB activation in a dose-dependent manner, whereas WIP1 knockdown resulted in increased NF-kappaB function. We show that WIP1 is a direct phosphatase of Ser 536 of the p65 subunit of NF-kappaB. Phosphorylation of Ser 536 is known to be essential for the transactivation function of p65, as it is required for recruitment of the transcriptional co-activator p300. WIP1-mediated regulation of p65 regulated binding of NF-kappaB to p300 and hence chromatin remodelling. Consistent with our results, mice lacking WIP1 showed enhanced inflammation. These results provide the first genetic proof that a phosphatase directly regulates NF-kappaB signalling in vivo. |
