Dissecting the Potential Interplay of DEK Functions in Inflammation and Cancer

Figure 1

DEK-mediated regulation of NFκB pathway activity in a dose-dependent manner. As DEK expression increases (red), canonical NFκB transcriptional activity decreases (blue). (a) In the absence of DEK, there is increased phosphorylation of IκBa, which leads to its degradation and the translocation of p65/RelA to the nucleus where it is transcribes proinflammatory target genes like MCP-1. (b) In cells with endogenous levels of DEK, possibly in both normal and transformed cells, DEK colocalization with p65 on target gene promoters is induced by TNFα treatment. This results in the expression of potentially oncogenic, prosurvival target genes like c-IAP2. However, it is unknown how variations in DEK levels within this group, such as the difference between normal and transformed cells, may impact NFκB activity and the subsequent expression of various target genes. (c) When DEK is substantially overexpressed beyond physiological levels, such as what may occur when overexpressing DEK in already high-expressing transformed cell lines, NFκB activity is inhibited, which may trigger cell death.