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|Title:||TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1.|
|Authors:||Etemadi, Nima;Chopin, Michael;Anderton, Holly;Tanzer, Maria C;Rickard, James A;Abeysekera, Waruni;Hall, Cathrine;Spall, Sukhdeep K;Wang, Bing;Xiong, Yuquan;Hla, Timothy;Pitson, Stuart M;Bonder, Claudine S;Wong, Wendy Wei-Lynn;Ernst, Matthias;Smyth, Gordon K;Vaux, David L;Nutt, Stephen L;Nachbur, Ueli;Silke, John|
|Affiliation:||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, Victoria, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, Australia
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
Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United States
Centre for Cancer Biology, SA Pathology, Adelaide, Australia
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland..
Department of Mathematics and Statistics, University of Melbourne, Parkville, Australia..
|Citation:||eLife 2015-12-23; 4|
|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.|
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
|Appears in Collections:||Journal articles|
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