Research ArticleCell Biology

The Endoplasmic Reticulum Acts as a Platform for Ubiquitylated Components of Nuclear Factor κB Signaling

Science Signaling  03 Sep 2013:
Vol. 6, Issue 291, pp. ra79
DOI: 10.1126/scisignal.2004496

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NF-κB Signals from the ER

As a first step in stimulating nuclear factor κB (NF-κB) signaling, plasma membrane–localized immunoreceptors accumulate adaptor proteins, ubiquitin ligases, and ubiquitylated proteins into complexes called signalosomes. Some of these factors are thought to detach from the complex to activate the cytosolic inhibitor of NF-κB (IκB) kinase (IKK) complex, which is required to release NF-κB dimers to translocate to the nucleus. Alexia et al. found that some ubiquitylated signalosome components were associated with the endoplasmic reticulum (ER), where they formed aggregates with the protein metadherin at the cytosolic leaflet. Loss of metadherin decreased NF-κB–dependent proinflammatory signaling in T and B cell lines that were activated through cytokine or antigen receptors. These findings suggest that metadherin acts as a focal point at the ER to transduce cell surface signals into biological responses.