ICEBERG: a novel inhibitor of interleukin-1beta generation.
Cell
; 103(1): 99-111, 2000 Sep 29.
Article
em En
| MEDLINE
| ID: mdl-11051551
ABSTRACT
ProIL-1beta is a proinflammatory cytokine that is proteolytically processed to its active form by caspase-1. Upon receipt of a proinflammatory stimulus, an upstream adaptor, RIP2, binds and oligomerizes caspase-1 zymogen, promoting its autoactivation. ICEBERG is a novel protein that inhibits generation of IL-1beta by interacting with caspase-1 and preventing its association with RIP2. ICEBERG is induced by proinflammatory stimuli, suggesting that it may be part of a negative feedback loop. Consistent with this, enforced retroviral expression of ICEBERG inhibits lipopolysaccharide-induced IL-1beta generation. The structure of ICEBERG reveals it to be a member of the death-domain-fold superfamily. The distribution of surface charge is complementary to the homologous prodomain of caspase-1, suggesting that charge-charge interactions mediate binding of ICEBERG to the prodomain of caspase-1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Sequência de Aminoácidos
/
Interleucina-1
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Proteínas Serina-Treonina Quinases
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Mediadores da Inflamação
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Caspase 1
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Peptídeos e Proteínas de Sinalização Intracelular
Idioma:
En
Revista:
Cell
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos