NF-kappaB mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism. Academic Article

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.

authors

• Sitcheran, Raquel

published proceedings

• Genes Dev

altmetric score

• 3

author list (cited authors)

• Sitcheran, R., Cogswell, P. C., & Baldwin, A. S.

citation count

• 108

complete list of authors

• Sitcheran, Raquel||Cogswell, Patricia C||Baldwin, Albert S

publication date

• October 2003

publisher

• Cold Spring Harbor Laboratory  Publisher

published in

• Genes and Development  Journal

keywords

• Animals
• Base Sequence
• Cell Differentiation
• Cells, Cultured
• Chondrocytes
• Conserved Sequence
• Down-Regulation
• High Mobility Group Proteins
• Mesoderm
• Mice
• MyoD Protein
• Myoblasts
• NF-kappa B
• RNA Interference
• RNA, Messenger
• Regulatory Sequences, Nucleic Acid
• SOX9 Transcription Factor
• Signal Transduction
• Transcription Factors

PubMed Central ID

• 14522944

Digital Object Identifier (DOI)

• 10.1101/gad.1114503

start page

• 2368

end page

• 2373

volume

• 17

issue

• 19

URL

• http://dx.doi.org/10.1101/gad.1114503