The NF-κB signaling pathway is involved in a broad range of biological processes including innate and adaptive immunity, inflammation, stress responses, B-cell development, and lymphoid organogenesis. A remarkable diversity of stimuli lead to the activation of NF-κB, among which are pro-inflammatory cytokines, LPS, growth factors, and antigen receptors. They activate an IKK complex (IKKβ, IKKα, and NEMO), which phosphorylates IκB proteins. Phosphorylation of IκB leads to its ubiquitination and proteasomal degradation, freeing NF-κB/Rel complexes. Active NF-κB/Rel complexes are further activated by phosphorylation and translocate to the nucleus where, either alone or in combination with other transcription factor families including AP-1, Ets, and Stat, they induce target gene expression[1],[2]. The core elements of NF-κB signaling pathways are generally several steps removed from the receptor itself. The intervening steps between receptor and IKK form links to parallel signaling pathways. For example, PKC enzymes play important roles in several signal transduction cascades. In NF-κB signaling, PKC-β connects the B cell receptor to canonical activation of NF-κB through a signaling complex, including Bcl10/MALT1 and NEMO/IKKγ[3].

[1] M.S. Hayden, S. Ghosh. Shared principles in NF-kappaB signaling. Cell. 2008, 132, 344-362.
[2]  Rel/NF-κB Transcription Factors. Gilmore TD. 2008.
[3] Protein Kinase C-β-Dependent Activation of NF-κB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo. G. Lutzny et al. Cancer Cell. 2013, 23, 77-92.

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2947 JTP 1048196 Prodrug of JTP 0819958; LUBAC inhibitor  Recently added €125.00
1888 ML 130 Potent and selective inhibitor of NOD1 (NLRC1) €95.00

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