@article{88111,
  keywords = {Humans, signal transduction, HeLa Cells, Cell Adhesion Molecules, Endoplasmic Reticulum, NF-kappa B, HEK293 Cells, Immunity, Innate, Adaptive Immunity, Ubiquitination, Cytokines, Jurkat Cells, Polyubiquitin},
  author = {Catherine Alexia and Konstantinos Poalas and Gabrielle Carvalho and Naima Zemirli and Julie Dwyer and Sonia Dubois and Emeline Hatchi and Nelia Cordeiro and Sherri Smith and C{\'e}line Castanier and Armelle Le Guelte and Liling Wan and Yibin Kang and Aim{\'e} Vazquez and Julie Gavard and Damien Arnoult and Nicolas Bid{\`e}re},
  title = {The endoplasmic reticulum acts as a platform for ubiquitylated components of nuclear factor κB signaling.},
  abstract = {<p>The innate and adaptive immune responses involve the stimulation of nuclear factor κB (NF-κB) transcription factors through the Lys(63) (K(63))-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 ER-anchored 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.</p>
},
  year = {2013},
  journal = {Sci Signal},
  volume = {6},
  pages = {ra79},
  month = {09/2013},
  issn = {1937-9145},
  doi = {10.1126/scisignal.2004496},
  language = {eng},
}