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Genes & Dev. 17 (19): 2368-2373

Copyright © 2003 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

NF-{kappa}B mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism

Raquel Sitcheran1, Patricia C. Cogswell1, and Albert S. Baldwin, Jr.1,2,3

1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
2 Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA

Abstract: Cytokines, such as tumor necrosis factor-{alpha} (TNF{alpha}), 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-{kappa}B controls TNF{alpha}-mediated suppression of myogenesis through a mechanism involving MyoD mRNA down-regulation. Here, we show that NF-{kappa}B 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-{kappa}B-mediated Sox9 and MyoD down-regulation. Thus, in response to cytokine signaling, NF-{kappa}B modulates the differentiation of mesenchymal-derived cell lineages via RNA sequence-dependent, posttranscriptional down-regulation of key developmental regulators.

Key Words: NF-{kappa}B • differentiation • mesenchymal • muscle • chondrocyte • posttranscriptional control

Received for publication May 19, 2003. Accepted for publication July 24, 2003.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1114503.

3 Corresponding author.
E-MAIL jhall{at}med.unc.edu; FAX (919) 966-8212.

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