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SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex

Author

Listed:
  • Fuminori Tokunaga

    (Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan)

  • Tomoko Nakagawa

    (Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan)

  • Masaki Nakahara

    (Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan)

  • Yasushi Saeki

    (Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan)

  • Masami Taniguchi

    (Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan)

  • Shin-ichi Sakata

    (Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan)

  • Keiji Tanaka

    (Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan)

  • Hiroyasu Nakano

    (Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan)

  • Kazuhiro Iwai

    (Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
    Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan)

Abstract

SHARPIN protein role in immune signalling The ubiquitin conjugation system regulates the canonical (or classical) nuclear factor κB (NF-κB)-activation pathway that mediates immune responses. Linear polyubiquitin chains, in which the C-terminal glycine of ubiquitin is conjugated to the amino group of the N-terminal methionine of another ubiquitin, is generated by a unique ubiquitin ligase complex called LUBAC — the linear ubiquitin chain assembly complex. LUBAC is composed of two RING domain proteins called HOIL-1 and HOIP. Now, three complementary studies published by the laboratories of Henning Walczak, Kazuhiro Iwai and Ivan Dikic identify a novel component of the LUBAC complex called SHARPIN, which is recruited to receptor signalling complexes that form following TNF and CD40L stimulation. The LUBAC complex containing SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo and is required for the activation of NF-κB signalling.

Suggested Citation

  • Fuminori Tokunaga & Tomoko Nakagawa & Masaki Nakahara & Yasushi Saeki & Masami Taniguchi & Shin-ichi Sakata & Keiji Tanaka & Hiroyasu Nakano & Kazuhiro Iwai, 2011. "SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex," Nature, Nature, vol. 471(7340), pages 633-636, March.
    • Handle: RePEc:nat:nature:v:471:y:2011:i:7340:d:10.1038_nature09815
    DOI: 10.1038/nature09815
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