independent of p38 MAPK since the p38 inhibitor, SB202190, did not rescue the heightened pS536-p65 levels in Wip1-depleted cells. Furthermore, overexpression of Wip1 inhibited the TNF-alpha-induced binding of p65 to its transcriptional cofactor p300. Finally, recombinant Wip1 dephosphorylated immunopurified pS536-p65 in an in vitro phosphatase assay, indicating that Wip1 can directly dephosphorylate pS536 of p65 (Table 1 and Figure 4). The authors concluded that Wip1 reduces the expression of cytokines such as TNFalpha after stimulation through inhibition of NF-kappaB activity (6).
