The endoplasmic reticulum acts as a platform for ubiquitylated components of nuclear factor κB signaling

Catherine Alexia, Konstantinos Poalas, Gabrielle Carvalho, Naima Zemirli, Julie Dwyer, Sonia M. Dubois, Emeline M. Hatchi, Nelia Cordeiro, Sherri S. Smith, Céline Castanier, Armelle Le Guelte, Liling Wan, Yibin Kang, Aimé Vazquez, Julie Gavard, Damien Arnoult, Nicolas Bidère

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22 Scopus citations

Abstract

The innate and adaptive immune responses involve the stimulation of nuclear factor κB (NF-κB) transcription factors through the Lys 63 (K63)-linked ubiquitylation of specific components of NF-κB signaling pathways. We found that ubiquitylated components of the NF-κB pathway accumulated on the cytosolic leaflet of the endoplasmic reticulum (ER) membrane after the engagement of cell-surface, proinflammatory cytokine receptors or antigen receptors. Through mass spectrometric analysis, we found that the ERanchored protein metadherin (MTDH) was a partner for these ubiquitylated activators of NF-κB and that it directly bound to K 63-linked polyubiquitin chains. Knockdown of MTDH inhibited the accumulation of ubiquitylated NF-κB signaling components at the ER, reduced the extent of NF-κB activation, and decreased the amount of proinflammatory cytokines produced. Our observations highlight an unexpected facet of the ER as a key subcellular gateway for NF-κB activation.

Original languageEnglish (US)
JournalScience Signaling
Volume6
Issue number291
DOIs
StatePublished - Sep 3 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Alexia, C., Poalas, K., Carvalho, G., Zemirli, N., Dwyer, J., Dubois, S. M., Hatchi, E. M., Cordeiro, N., Smith, S. S., Castanier, C., Le Guelte, A., Wan, L., Kang, Y., Vazquez, A., Gavard, J., Arnoult, D., & Bidère, N. (2013). The endoplasmic reticulum acts as a platform for ubiquitylated components of nuclear factor κB signaling. Science Signaling, 6(291). https://doi.org/10.1126/scisignal.2004496