Deubiquitinases A20 and CYLD modulate costimulatory signaling via CD137 (4–1BB)
| Autor: | Arantza Azpilikueta, Elixabet Bolaños, Valerie Lang, Sara Labiano, Maria A. Aznar, Iñaki Etxeberria, Alvaro Teijeira, Maria E. Rodriguez-Ruiz, Jose L. Perez-Gracia, Maria Jure-Kunkel, Juan M. Zapata, Manuel S. Rodriguez, Ignacio Melero |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | OncoImmunology, Vol 7, Iss 1 (2018) |
| Druh dokumentu: | article |
| ISSN: | 2162-402X 2162402X |
| DOI: | 10.1080/2162402X.2017.1368605 |
| Popis: | TRAF2 dependent K63-polyubiquitinations have been recently shown to connect CD137 (4–1BB) stimulation to NF-κB activation. In a search of deubiquitinase enzymes (DUBs) that could regulate such a signaling route, A20 and CYLD were found to coimmunoprecipitate with CD137 and TRAF2 complexes. Indeed, overexpression of A20 or CYLD downregulated CD137-elicited ubiquitination of TRAF2 and TAK1 upon stimulation with agonist monoclonal antibodies. Moreover, overexpression of A20 or CYLD downregulated CD137-induced NF-κB activation in cultured cells and in gene-transferred hepatocytes in vivo, while silencing these deubiquitinases enhanced CD137 costimulation of primary human CD8 T cells. Therefore A20 and CYLD directly downregulate the signaling from a T and NK-cell costimulatory receptor under exploitation for cancer immunotherapy in clinical trials. |
| Databáze: | Directory of Open Access Journals |
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