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SHARPIN forms a lin...
SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis.
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- Ikeda, Fumiyo (författare)
- 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
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- Deribe, Yonathan Lissanu (författare)
- 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
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- Skånland, Sigrid S (författare)
- 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
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- Stieglitz, Benjamin (författare)
- MRC-National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
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- Grabbe, Caroline (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),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
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- Franz-Wachtel, Mirita (författare)
- Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
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- van Wijk, Sjoerd J L (författare)
- 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
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- Goswami, Panchali (författare)
- 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
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- Nagy, Vanja (författare)
- IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohrgasse 3, 1030 Vienna, Austria
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- Terzic, Janos (författare)
- School of Medicine, University of Split, Soltanska 2, Split, HR-21000, Croatia
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- Tokunaga, Fuminori (författare)
- Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
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- Androulidaki, Ariadne (författare)
- 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
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- Nakagawa, Tomoko (författare)
- Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
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- Pasparakis, Manolis (författare)
- 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
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- Iwai, Kazuhiro (författare)
- Department of Biophysics and Biochemistry, 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
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- Sundberg, John P (författare)
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
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- Schaefer, Liliana (författare)
- Allgemeine Pharmakologie und Toxikologie, Division Nephropharmakologie, Klinikum der Goethe Universität, Theodor-Stern Kai 7, 60590 Frankfurt, Germany
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- Rittinger, Katrin (författare)
- MRC-National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
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- Macek, Boris (författare)
- Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
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- Dikic, Ivan (författare)
- 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
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(creator_code:org_t)
- 2011-03-30
- 2011
- Engelska.
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 471:7340, s. 637-641
- Relaterad länk:
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https://europepmc.or...
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Abstract
Ämnesord
Stäng
- SHARPIN is a ubiquitin-binding and ubiquitin-like-domain-containing protein which, when mutated in mice, results in immune system disorders and multi-organ inflammation. Here we report that SHARPIN functions as a novel component of the linear ubiquitin chain assembly complex (LUBAC) and that the absence of SHARPIN causes dysregulation of NF-κB and apoptotic signalling pathways, explaining the severe phenotypes displayed by chronic proliferative dermatitis (cpdm) in SHARPIN-deficient mice. Upon binding to the LUBAC subunit HOIP (also known as RNF31), SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo. Coexpression of SHARPIN and HOIP promotes linear ubiquitination of NEMO (also known as IKBKG), an adaptor of the IκB kinases (IKKs) and subsequent activation of NF-κB signalling, whereas SHARPIN deficiency in mice causes an impaired activation of the IKK complex and NF-κB in B cells, macrophages and mouse embryonic fibroblasts (MEFs). This effect is further enhanced upon concurrent downregulation of HOIL-1L (also known as RBCK1), another HOIP-binding component of LUBAC. In addition, SHARPIN deficiency leads to rapid cell death upon tumour-necrosis factor α (TNF-α) stimulation via FADD- and caspase-8-dependent pathways. SHARPIN thus activates NF-κB and inhibits apoptosis via distinct pathways in vivo.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- biology
- biologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Ikeda, Fumiyo
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Deribe, Yonathan ...
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Skånland, Sigrid ...
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Stieglitz, Benja ...
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Grabbe, Caroline
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Franz-Wachtel, M ...
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van Wijk, Sjoerd ...
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Goswami, Panchal ...
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Nagy, Vanja
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Terzic, Janos
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Tokunaga, Fumino ...
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Androulidaki, Ar ...
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Nakagawa, Tomoko
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Pasparakis, Mano ...
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Iwai, Kazuhiro
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Sundberg, John P
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Schaefer, Lilian ...
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Rittinger, Katri ...
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Macek, Boris
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Dikic, Ivan
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