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

Fuminori Tokunaga, Tomoko Nakagawa, Masaki Nakahara, Yasushi Saeki, Masami Taniguchi, Shin-ichi Sakata, Keiji Tanaka, Hiroyasu Nakano and Kazuhiro Iwai ()
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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

Nature, 2011, vol. 471, issue 7340, 633-636

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.

Date: 2011
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DOI: 10.1038/nature09815

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