Regulation of NFKB signaling by the proteasome

Regulation of NF-κB signaling by the proteasome. Multiple inflammatory signals result in the activation of the transcription factor NF-κB through a variety of adapter proteins and kinases. The most abundant form of the NF-κB dimer is the p50/p65 heterodimer. (A) The p105 precursor is processed by the proteasome, thereby liberating the NF-kB p50 subunit for dimerization with p65. IκB retains the NF-κB heterodimer in the cytoplasm. (B) Ligand binding to cellular receptors like TLRs activates the IKK complex, which catalyzes the phosphorylation of IκB, inducing its poly-ubiquitination and degradation by the proteasome. (C) Activated NF-κB translocates into the nucleus, where it (D) activates target gene expression. Table summarizes all reported effects of i-proteasome activity on the different steps in this canonical NF-κB signaling pathway. NF-kB, nuclear factor kappa B; IκBs, inhibitors of κB; IKK, IκB kinase.

Publication

Proteasomal Protein Degradation: Adaptation of Cellular Proteolysis With Impact on Virus—and Cytokine-Mediated Damage of Heart Tissue During Myocarditis. (2018) Antje Beling, et al. Front Immunol. 2018;9:2620. Figure: F2. All organisms Homo sapiens Mus musculus Drosophila melanogaster

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