Twist regulates cytokine gene expression through a negative feedback loop that represses NF-κB activity

Dražen Šošić, James A. Richardson, Kai Yu, David M. Ornitz, Eric N. Olson

Research output: Contribution to journalArticle

313 Scopus citations

Abstract

During Drosophila embryogenesis, the dorsal transcription factor activates the expression of twist, a transcription factor required for mesoderm formation. We show here that the mammalian twist proteins, twist-1 and -2, are induced by a cytokine signaling pathway that requires the dorsal-related protein RelA, a member of the NF-κB family of transcription factors. Twist-1 and -2 repress cytokine gene expression through interaction with RelA. Mice homozygous for a twist-2 null allele or doubly heterozygous for twist-1 and -2 alleles show elevated expression of proinflammatory cytokines, resulting in perinatal death from cachexia. These findings reveal an evolutionarily conserved signaling circuit in which twist proteins regulate cytokine signaling by establishing a negative feedback loop that represses the NF-κB-dependent cytokine pathway.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalCell
Volume112
Issue number2
DOIs
StatePublished - Jan 24 2003

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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