Go to page
 

Bibliographic Metadata

Title
EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
AuthorMutz, Cornelia N. ; Schwentner, Raphaela ; Kauer, Maximilian O. ; Katschnig, Anna M. ; Kromp, Florian ; Aryee, Dave N. T. ; Erhardt, Sophie ; Goiny, Michel ; Alonso, Javier ; Fuchs, Dietmar ; Kovar, Heinrich
Published in
FEBS Letters, Hoboken, 2016, Vol. 590, Issue 14, page 2063-2075
PublishedHoboken : Wiley-Blackwell, 2016
LanguageEnglish
Document typeJournal Article
Keywords (DE)aryl hydrocarbon receptor / EWS-FLI1 / tryptophan / cell-cycle regulation / indoleamine 2,3-dioxygenase / ewing sarcoma / gene-expression / tumor-growth / ah receptor / rna interference / in-vitro / cancer / acid
Project-/ReportnumberI 1225-B19
ISSN0014-5793
URNurn:nbn:at:at-ubmuw:3-1508 Persistent Identifier (URN)
DOI10.1002/1873-3468.12243 
Restriction-Information
 The work is publicly available
Files
EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway [0.54 mb]
Links
Reference
Classification
Abstract (English)

Ewing sarcoma (ES) is an aggressive pediatric tumor driven by the fusion protein EWS-FLI1. We report that EWS-FLI1 suppresses TDO2-mediated tryptophan (TRP) breakdown in ES cells. Gene expression and metabolite analyses reveal an EWS-FLI1-dependent regulation of TRP metabolism. TRP consumption increased in the absence of EWS-FLI1, resulting in kynurenine and kynurenic acid accumulation, both aryl hydrocarbon receptor (AHR) ligands. Activated AHR binds to the promoter region of target genes. We demonstrate that EWS-FLI1 knockdown results in AHR nuclear translocation and activation. Our data suggest that EWS-FLI1 suppresses autocrine AHR signaling by inhibiting TDO2-catalyzed TRP breakdown.

Stats
The PDF-Document has been downloaded 3 times.
License
CC-BY-License (4.0)Creative Commons Attribution 4.0 International License