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

D Šošić, JA Richardson, K Yu, DM Ornitz, EN Olson - Cell, 2003 - cell.com
D Šošić, JA Richardson, K Yu, DM Ornitz, EN Olson
Cell, 2003cell.com
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 …
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.
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