核因子-κB通过转录后基因沉默机制介导间充质细胞分化的抑制。
NF-kappaB mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism.
作者信息
Sitcheran Raquel, Cogswell Patricia C, Baldwin Albert S
机构信息
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
出版信息
Genes Dev. 2003 Oct 1;17(19):2368-73. doi: 10.1101/gad.1114503.
Abstract
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.
摘要
细胞因子，如肿瘤坏死因子-α（TNFα），能有效抑制间充质细胞的分化，并下调软骨细胞和肌细胞发育所需的转录因子Sox9和MyoD的表达。此前，我们证明NF-κB通过一种涉及MyoD mRNA下调的机制来控制TNFα介导的肌生成抑制。在此，我们表明NF-κB也抑制软骨生成并使Sox9 mRNA水平不稳定。mRNA顺式调节基序（5'-ACUACAG-3'）的多个拷贝对于NF-κB介导的Sox9和MyoD下调是必要且充分的。因此，响应细胞因子信号，NF-κB通过关键发育调节因子的RNA序列依赖性、转录后下调来调节间充质来源细胞谱系的分化。
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