SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis

Fumiyo Ikeda, Yonathan Lissanu Deribe, Sigrid S. Skånland, Benjamin Stieglitz, Caroline Grabbe, Mirita Franz-Wachtel, Sjoerd J. L. van Wijk, Panchali Goswami, Vanja Nagy, Janos Terzic, Fuminori Tokunaga, Ariadne Androulidaki, Tomoko Nakagawa, Manolis Pasparakis, Kazuhiro Iwai, John P. Sundberg, Liliana Schaefer, Katrin Rittinger, Boris Macek and Ivan Dikic ()
Additional contact information
Fumiyo Ikeda: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
Yonathan Lissanu Deribe: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
Sigrid S. Skånland: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
Benjamin Stieglitz: MRC-National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Caroline Grabbe: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
Mirita Franz-Wachtel: Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
Sjoerd J. L. van Wijk: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
Panchali Goswami: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany
Vanja Nagy: IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohrgasse 3, 1030 Vienna, Austria
Janos Terzic: School of Medicine, University of Split, Soltanska 2, Split, HR-21000, Croatia
Fuminori Tokunaga: Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
Ariadne Androulidaki: Institute for Genetics, Centre for Molecular Medicine (CMMC), and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Str. 47a, 50674 Cologne, Germany
Tomoko Nakagawa: Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
Manolis Pasparakis: Institute for Genetics, Centre for Molecular Medicine (CMMC), and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Str. 47a, 50674 Cologne, Germany
Kazuhiro Iwai: Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
John P. Sundberg: The Jackson Laboratory
Liliana Schaefer: Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe Universität, Theodor-Stern Kai 7, 60590 Frankfurt, Germany
Katrin Rittinger: MRC-National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Boris Macek: Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
Ivan Dikic: Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany

Nature, 2011, vol. 471, issue 7340, 637-641

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/nature09814

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