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Title: The role of NF-kB and histone deacetylase in gene regulation
Keywords: role, NF-kB, NF-kappaB, histone deacetylase, HDAC, gene regulation
Issue Date: 10-Aug-2009
Source: CHEW SOO FEN, JOANNE CHRISTABELLE (2009-08-10). The role of NF-kB and histone deacetylase in gene regulation. ScholarBank@NUS Repository.
Abstract: Post-translational modifications of NF-kB via phosphorylations enhance the transactivation potential of NF-kB. Much is known about the kinases that phosphorylate NF-kB, but little is known about the phosphatases that dephosphorylate NF-kB. Here, we report the regulation of NF-kB by the WIP1 phosphatase and its role in inflammation. Overexpression of WIP1 in HeLa cervical cancer and Saos-2 osteoscarcoma cells results in decreased NF-kB activation in a manner dependent on the dosage of WIP1. Overexpression of WIP1 could also repress the expression of endogenous NF-kB target genes in response to inflammatory stimuli. Conversely, knockdown of WIP1 results in increased NF-kB transcriptional function. To investigate the molecular mechanism by which WIP1 regulates NF-kB function, we investigated whether WIP1 can dephosphorylate any component of the NF-kB signaling cascade. Using in vitro and in vivo experiments, we demonstrate that WIP1 is a direct phosphatase on serine 536 of the p65 subunit of NF-kB.
Appears in Collections:Ph.D Theses (Open)

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