Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity.
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-kappaB 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-kappaB-dependent cytokine pathway.
Mesh Terms:
Animals, Apoptosis, Cachexia, Cytokines, Feedback, Physiological, Gene Expression Regulation, Developmental, Genes, Lethal, Inflammation, Mice, Mice, Knockout, Mutation, NF-kappa B, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Signal Transduction, Skin, Transcription Factor RelA, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Necrosis Factor-alpha, Twist Transcription Factor
Animals, Apoptosis, Cachexia, Cytokines, Feedback, Physiological, Gene Expression Regulation, Developmental, Genes, Lethal, Inflammation, Mice, Mice, Knockout, Mutation, NF-kappa B, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Signal Transduction, Skin, Transcription Factor RelA, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Necrosis Factor-alpha, Twist Transcription Factor
Cell
Date: Jan. 24, 2003
PubMed ID: 12553906
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