1. Biochemistry and Chemical Biology
  2. Immunology and Inflammation
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TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase-1

  1. Nima Etemadi
  2. Michael Chopin
  3. Holly Anderton
  4. Maria C Tanzer
  5. James A Rickard
  6. Waruni Abeysekra
  7. Cathrine Hall
  8. Sukhdeep K Spall
  9. Bing Wang
  10. Yuquan Xiong
  11. Timothy Hla
  12. Stuart M Pitson
  13. Claudine S Bonder
  14. Wendy Wei-Lynn Wong
  15. Matthias Ernst
  16. Gordon K Smyth
  17. David L Vaux
  18. Stephen L Nutt
  19. Ueli Nachbur
  20. John Silke  Is a corresponding author
  1. Walter and Eliza Hall Institute of Medical Research, Australia
  2. Monash University, Australia
  3. Cornell University, United States
  4. SA Pathology, Australia
  5. University of Zurich, Switzerland
  6. Olivia Newton-John Cancer Research Institute, Australia
Research Article
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Cite this article as: eLife 2015;4:e10592 doi: 10.7554/eLife.10592

Abstract

TRAF2 is a component of TNF superfamily signalling complexes and plays an essential role in the regulation and homeostasis of immune cells. TRAF2 deficient mice die around birth, therefore its role in adult tissues is not well-explored. Furthermore, the role of the TRAF2 RING is controversial. It has been claimed that the atypical TRAF2 RING cannot function as a ubiquitin E3 ligase but counterclaimed that TRAF2 RING requires a co-factor, sphingosine-1-phosphate, that is generated by the enzyme sphingosine kinase-1, to function as an E3 ligase. Keratinocyte specific deletion of Traf2, but not Sphk1 deficiency, disrupted TNF mediated NF-κB and MAP kinase signalling and caused epidermal hyperplasia and psoriatic skin inflammation. This inflammation was driven by TNF, cell death, non-canonical NF-κB and the adaptive immune system and might therefore represent a clinically relevant model of psoriasis. TRAF2 therefore has essential tissue specific functions that do not overlap with those of Sphk1.

Article and author information

Author details

  1. Nima Etemadi

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael Chopin

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Holly Anderton

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Maria C Tanzer

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. James A Rickard

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Waruni Abeysekra

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Cathrine Hall

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Sukhdeep K Spall

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Bing Wang

    Center for Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Yuquan Xiong

    Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Timothy Hla

    Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Stuart M Pitson

    Centre for Cancer Biology, SA Pathology, Adelaide, Australia
    Competing interests
    The authors declare that no competing interests exist.
  13. Claudine S Bonder

    Centre for Cancer Biology, SA Pathology, Adelaide, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Wendy Wei-Lynn Wong

    Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  15. Matthias Ernst

    Olivia Newton-John Cancer Research Institute, Heidelberg, Australia
    Competing interests
    The authors declare that no competing interests exist.
  16. Gordon K Smyth

    Bioinformatics, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. David L Vaux

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  18. Stephen L Nutt

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  19. Ueli Nachbur

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  20. John Silke

    Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    For correspondence
    j.silke@latrobe.edu.au
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Mice were maintained at the Walter and Eliza Hall Institute (WEHI) under the approval of WEHI ethics committee and Institute guidelines. All procedures were specifcally approved under WEHI Ethics Project Number 2011.013 and 2014.015.

Reviewing Editor

  1. Ivan Dikic, Goethe University Medical School, Germany

Publication history

  1. Received: August 4, 2015
  2. Accepted: December 21, 2015
  3. Accepted Manuscript published: December 23, 2015 (version 1)
  4. Version of Record published: February 16, 2016 (version 2)
  5. Version of Record updated: June 27, 2017 (version 3)

Copyright

© 2015, Etemadi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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