| First Author | Sitcheran R | Year | 2003 |
| Journal | Genes Dev | Volume | 17 |
| Issue | 19 | Pages | 2368-73 |
| PubMed ID | 14522944 | Mgi Jnum | J:85993 |
| Mgi Id | MGI:2677651 | Doi | 10.1101/gad.1114503 |
| Citation | Sitcheran R, et al. (2003) NF-kappaB mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism. Genes Dev 17(19):2368-73 |
| abstractText | 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. |
