STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling.
Nat Immunol
; 15(2): 168-76, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24413774
ABSTRACT
STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. Type 2 interferon-mediated transcription and antibacterial immunity essentially disappeared owing to defective promoter recruitment of GAF. In contrast, STAT1 recruitment to ISGF3 binding sites and type 1 interferon-dependent responses, including antiviral protection, remained intact. We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
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Interferon gama
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Fator de Transcrição STAT1
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Proteínas Mutantes
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article