Free p65 can protect against TNF-Alpha-induced apoptosis in the absence of IKK activity

(A) Free p65 can protect against TNF-α-induced apoptosis in the absence of IKK activity. IKK1/2−/− MEFs transduced with LV-GFP or LV-GFP-p65 were treated with TNF-α, 48 h after transduction. Cell survival was estimated by staining the cells with crystal violet 48 h after TNF-α treatment. (B) Subcellular localization of GFP-p65. Live IKK1/2−/− cells transduced with LV-GFP or LV-GFP-p65 were imaged at ×60 magnification by using a deconvolution microscope. (C) Model based on our studies. Cytokines such as TNF-α and interleukin-1 primarily employ IKK2, and lymphotoxin β (LTβ) and RANK ligand (RANKL) use IKK1 to activate NF-κB. Unlike these stimuli, DoxR can activate NF-κB in an IKK1- and IKK2-independent manner. Despite their different origins, all of the pathways of NF-κB activation are blocked by proteasome inhibitors. Based on data presented in this report, functional activation by p65/p50 complexes (shown in red) generated after TNF-α signaling (A) or DoxR induction (Fig. ) do not require further modification by IKK1 or IKK2.

Publication

IκB Kinase-Independent IκBα Degradation Pathway: Functional NF-κB Activity and Implications for Cancer Therapy. (2003) Vinay Tergaonkar, et al. Mol Cell Biol. 2003 Nov;23(22):8070-8083. Figure: F9. All organisms Homo sapiens Drosophila melanogaster Danio rerio

Disease mentions