Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Heidelberg, Australia
Michael Chopin
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
Holly Anderton
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
Maria C Tanzer
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
James A Rickard
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
Waruni Abeysekera
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Cathrine Hall
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Sukhdeep K Spall
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
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
Yuquan Xiong
Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United States
Timothy Hla
Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United States
Stuart M Pitson
Centre for Cancer Biology, SA Pathology, Adelaide, Australia
Claudine S Bonder
Centre for Cancer Biology, SA Pathology, Adelaide, Australia
Wendy Wei-Lynn Wong
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
Matthias Ernst
Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Heidelberg, Australia
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Mathematics and Statistics, University of Melbourne, Parkville, Australia
David L Vaux
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
Ueli Nachbur
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
John Silke
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
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.
