Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2

Sergio E. Alvarez, Kuzhuvelil B. Harikumar, Nitai C. Hait, Jeremy Allegood, Graham M. Strub, Eugene Y. Kim, Michael Maceyka, Hualiang Jiang, Cheng Luo, Tomasz Kordula, Sheldon Milstien and Sarah Spiegel ()
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Sergio E. Alvarez: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Kuzhuvelil B. Harikumar: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Nitai C. Hait: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Jeremy Allegood: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Graham M. Strub: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Eugene Y. Kim: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Michael Maceyka: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Hualiang Jiang: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Cheng Luo: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Tomasz Kordula: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Sheldon Milstien: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA
Sarah Spiegel: Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA

Nature, 2010, vol. 465, issue 7301, 1084-1088

Abstract: A cofactor for the E3 ubiquitin ligase TRAF2 TRAF2 (tumour-necrosis factor receptor-associated factor 2), a component of the NF-κB activation pathway important in inflammatory, anti-apoptotic, and immune processes, is shown to be a target of sphingosine kinase 1, one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate inside cells. In addition, sphingosine kinase 1 is revealed as the 'missing' cofactor for TRAF2 E3 ubiquitin ligase activity. These findings provide a mechanistic explanation for the numerous observations of the importance of SphK1 in inflammatory, anti-apoptotic and immune processes.

Date: 2010
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DOI: 10.1038/nature09128

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