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J Immunol. 2020 Mar 1;204(5):1085-1090. doi: 10.4049/jimmunol.1901260. Epub 2020 Jan 22.

Cutting Edge: The RNA-Binding Protein Ewing Sarcoma Is a Novel Modulator of Lymphotoxin β Receptor Signaling.

Author information

1
Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.
2
National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.
3
Department of Immunology and Respiratory Disease Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
4
Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; cware@sbpdiscovery.org.

Abstract

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.

PMID:
31969387
DOI:
10.4049/jimmunol.1901260

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