Please use this identifier to cite or link to this item:
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.
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
ISSN: 14657392
DOI: 10.1038/ncb1873
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Oct 19, 2021


checked on Oct 19, 2021

Page view(s)

checked on Oct 14, 2021

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.