Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncb1873
Title: WIP1 phosphatase is a negative regulator of NF-κB signalling
Authors: Chew, J.
Biswas, S. 
Shreeram, S.
Humaidi, M.
Wong, E.T.
Dhillion, M.K.
Teo, H.
Hazra, A.
Fang, C.C.
López-Collazo, E.
Bulavin, D.V.
Tergaonkar, V. 
Issue Date: 2009
Citation: Chew, J., Biswas, S., Shreeram, S., Humaidi, M., Wong, E.T., Dhillion, M.K., Teo, H., Hazra, A., Fang, C.C., López-Collazo, E., Bulavin, D.V., Tergaonkar, V. (2009). WIP1 phosphatase is a negative regulator of NF-κB signalling. Nature Cell Biology 11 (5) : 659-666. ScholarBank@NUS Repository. https://doi.org/10.1038/ncb1873
Abstract: Post-translational modifications of NF-κB through phosphorylations enhance its transactivation potential. Much is known about the kinases that phosphorylate NF-κB, 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-κB signalling. WIP1-mediated regulation of NF-κB occurs in both a p38-dependent and independent manner. Overexpression of WIP1 resulted in decreased NF-κB activation in a dose-dependent manner, whereas WIP1 knockdown resulted in increased NF-κB function. We show that WIP1 is a direct phosphatase of Ser 536 of the p65 subunit of NF-κB. 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-κB 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-κB signalling in vivo.
Source Title: Nature Cell Biology
URI: http://scholarbank.nus.edu.sg/handle/10635/107737
ISSN: 14657392
DOI: 10.1038/ncb1873
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