Cutting Edge: The RNA-Binding Protein Ewing Sarcoma Is a Novel Modulator of Lymphotoxin β Receptor Signaling.
Richard Virgen-SlaneRicardo G CorreaParham Ramezani-RadSeth Steen-FuentesThiago DetanicoMichael J DiCandidoJun LiCarl F WarePublished in: Journal of immunology (Baltimore, Md. : 1950) (2020)
Lymphotoxin β receptor (LTβR) signaling is crucial for lymphoid tissue organogenesis and immune homeostasis. To identify novel regulatory mechanisms for signaling, we implemented a two-step screen that uses coexpression analysis of human fibroblasts undergoing LTβR stimulation and affinity-purification mass spectrometry for the LTβR signaling protein TNFR-associated factor 3 (TRAF3). We identify Ewing sarcoma (EWS) protein as a novel LTβR signaling component that associates with TRAF3 but not with TNFR-associated factor 2 (TRAF2). The EWS:TRAF3 complex forms under unligated conditions that are disrupted following activation of the LTβR. We conclude that EWS limits expression of proinflammatory molecules, GM-CSF, and ERK-2, promoting immune homeostasis.
Keyphrases
- binding protein
- mass spectrometry
- endothelial cells
- poor prognosis
- signaling pathway
- high throughput
- cell proliferation
- amino acid
- protein protein
- high resolution
- extracellular matrix
- resting state
- liquid chromatography
- capillary electrophoresis
- single cell
- high performance liquid chromatography
- gas chromatography
- functional connectivity
- tandem mass spectrometry
- nucleic acid