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

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  • 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
    Umeå University, Building 6L, 901 87 Umeå, Sweden)

  • 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
    Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, 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
    School of Medicine, University of Split, Soltanska 2, Split, HR-21000, Croatia)

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

  • 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 & Fumin, 2011. "SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis," Nature, Nature, vol. 471(7340), pages 637-641, March.
  • Handle: RePEc:nat:nature:v:471:y:2011:i:7340:d:10.1038_nature09814
    DOI: 10.1038/nature09814
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    Citations

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    Cited by:

    1. Xiangyi S. Wang & Thomas R. Cotton & Sarah J. Trevelyan & Lachlan W. Richardson & Wei Ting Lee & John Silke & Bernhard C. Lechtenberg, 2023. "The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Hannah Schünke & Ulrike Göbel & Ivan Dikic & Manolis Pasparakis, 2021. "OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Lining Lu & Xiaoguo Zhai & Xiaolong Li & Shuansuo Wang & Lijun Zhang & Luyang Wang & Xi Jin & Lujun Liang & Zhiheng Deng & Zichen Li & Yanfeng Wang & Xiangdong Fu & Honggang Hu & Jiawei Wang & Ziqing , 2022. "Met1-specific motifs conserved in OTUB subfamily of green plants enable rice OTUB1 to hydrolyse Met1 ubiquitin chains," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Yi Luan & Wenying Long & Lisi Dai & Panfeng Tao & Zhifen Deng & Zongping Xia, 2024. "Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Esther Hoste & Kim Lecomte & Karl Annusver & Niels Vandamme & Jana Roels & Sophia Maschalidi & Lien Verboom & Hanna-Kaisa Vikkula & Mozes Sze & Lisette Van Hove & Kevin Verstaen & Arne Martens & Tino , 2021. "OTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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