TY - JOUR
T1 - Twist regulates cytokine gene expression through a negative feedback loop that represses NF-κB activity
AU - Šošić, Dražen
AU - Richardson, James A.
AU - Yu, Kai
AU - Ornitz, David M.
AU - Olson, Eric N.
N1 - Funding Information:
We thank Richard Behringer and Patrick Tam for twist-1 mutant mice; James Chen for p50 and p65 cDNAs; Amer Beg for p65 −/− cells; Chris Pomajzl, Jeff Stark, and John Shelton for histology; Li Li and Chris Davis for advice; and Alisha Tizenor for graphic assistance. We also thank James Chen and Tim McKinsey for critically reading the manuscript. Supported by grants from NIH to E.N.O. and by NIH grant HD39952 to D.M.O.
PY - 2003/1/24
Y1 - 2003/1/24
N2 - 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.
AB - 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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U2 - 10.1016/S0092-8674(03)00002-3
DO - 10.1016/S0092-8674(03)00002-3
M3 - Article
C2 - 12553906
AN - SCOPUS:0037462477
SN - 0092-8674
VL - 112
SP - 169
EP - 180
JO - Cell
JF - Cell
IS - 2
ER -