pLxIS-containing domains are biochemically flexible regulators of interferons and metabolism.
Mol Cell
; 84(13): 2436-2454.e10, 2024 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-38925114
ABSTRACT
Signal transduction proteins containing a pLxIS motif induce interferon (IFN) responses central to antiviral immunity. Apart from their established roles in activating the IFN regulator factor (IRF) transcription factors, the existence of additional pathways and functions associated with the pLxIS motif is unknown. Using a synthetic biology-based platform, we identified two orphan pLxIS-containing proteins that stimulate IFN responses independent of all known pattern-recognition receptor pathways. We further uncovered a diversity of pLxIS signaling mechanisms, where the pLxIS motif represents one component of a multi-motif signaling entity, which has variable functions in activating IRF3, the TRAF6 ubiquitin ligase, IκB kinases, mitogen-activated protein kinases, and metabolic activities. The most diverse pLxIS signaling mechanisms were associated with the highest antiviral activities in human cells. The flexibility of domains that regulate IFN signaling may explain their prevalence in nature.
Palavras-chave
GMIP; IRSp53; MAVS; MyD88; STING; TASL; TBK1; TRAF6; TRIF; infection; interferon; macrophages; synthetic biology
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Interferons
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Fator 6 Associado a Receptor de TNF
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Fator Regulador 3 de Interferon
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article