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

310 Citations (Scopus)

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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Twist-Related Protein 1
Gene expression
Cytokines
Feedback
Gene Expression
Transcription Factors
Alleles
Cachexia
Mesoderm
Drosophila
Embryonic Development
Networks (circuits)
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Twist regulates cytokine gene expression through a negative feedback loop that represses NF-κB activity. / Šošić, Dražen; Richardson, James A.; Yu, Kai; Ornitz, David M.; Olson, Eric N.

In: Cell, Vol. 112, No. 2, 24.01.2003, p. 169-180.

Research output: Contribution to journalArticle

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