NF-κB mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism
NF-κB mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism
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DOI：
10.1101/gad.1114503
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发表时间：
2003-10-01
影响因子：
10.5
通讯作者：
Baldwin, AS
中科院分区：
文献类型：
--
作者：
Sitcheran, R;Cogswell, PC;Baldwin, AS
Cytokines, such as tumor necrosis factor-alpha (TNFalpha), potently inhibit the differentiation of mesenchymal cells and down-regulate the expression of Sox9 and MyoD, transcription factors required for chondrocyte and myocyte development. Previously, we demonstrated that NF-kappaB controls TNFalpha-mediated suppression of myogenesis through a mechanism involving MyoD mRNA down-regulation. Here, we show that NF-kappaB also suppresses chondrogenesis and destabilizes Sox9 mRNA levels. Multiple copies of an mRNA cis-regulatory motif (5'-ACUACAG-3') are necessary and sufficient for NF-kappaB-mediated Sox9 and MyoD down-regulation. Thus, in response to cytokine signaling, NF-kappaB modulates the differentiation of mesenchymal-derived cell lineages via RNA sequence-dependent, posttranscriptional down-regulation of key developmental regulators.
