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


Journal

Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R

Informations de publication

Date de publication:
01 03 2020
Historique:
received: 24 10 2019
accepted: 22 12 2019
pubmed: 24 1 2020
medline: 9 9 2020
entrez: 24 1 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31969387
pii: jimmunol.1901260
doi: 10.4049/jimmunol.1901260
pmc: PMC7033016
mid: NIHMS1547578
doi:

Substances chimiques

EWSR1 protein, human 0
LTBR protein, human 0
Lymphotoxin beta Receptor 0
Multiprotein Complexes 0
PSMD2 protein, human 0
RNA-Binding Protein EWS 0
TNF Receptor-Associated Factor 2 0
TNF Receptor-Associated Factor 3 0
TRAF3 protein, human 0
Granulocyte-Macrophage Colony-Stimulating Factor 83869-56-1
MAPK1 protein, human EC 2.7.11.24
Mitogen-Activated Protein Kinase 1 EC 2.7.11.24

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1085-1090

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI067890
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR064194
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA177322
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA164679
Pays : United States

Informations de copyright

Copyright © 2020 by The American Association of Immunologists, Inc.

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Auteurs

Richard Virgen-Slane (R)

Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.

Ricardo G Correa (RG)

Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.

Parham Ramezani-Rad (P)

National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.

Seth Steen-Fuentes (S)

Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.

Thiago Detanico (T)

Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.

Michael J DiCandido (MJ)

Department of Immunology and Respiratory Disease Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.

Jun Li (J)

Department of Immunology and Respiratory Disease Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.

Carl F Ware (CF)

Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; cware@sbpdiscovery.org.

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