Ribosomal Protein S3: A KH Domain Subunit in NF-κB Complexes that Mediates Selective Gene Regulation

Fengyi Wan, D. Eric Anderson, Robert A. Barnitz, Andrew Snow, Nicolas Bidere, Lixin Zheng, Vijay Hegde, Lloyd T. Lam, Louis M. Staudt, David Levens, Walter A. Deutsch, Michael J. Lenardo

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

NF-κB is a DNA-binding protein complex that transduces a variety of activating signals from the cytoplasm to specific sets of target genes. To understand the preferential recruitment of NF-κB to specific gene regulatory sites, we used NF-κB p65 in a tandem affinity purification and mass spectrometry proteomic screen. We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding. RPS3 knockdown impaired NF-κB-mediated transcription of selected p65 target genes but not nuclear shuttling or global protein translation. Rather, lymphocyte-activating stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF-κB bound to specific regulatory sites in chromatin. Thus, RPS3 is an essential but previously unknown subunit of NF-κB involved in the regulation of key genes in rapid cellular activation responses. Our observations provide insight into how NF-κB selectively controls gene expression.

Original languageEnglish
Pages (from-to)927-939
Number of pages13
JournalCell
Volume131
Issue number5
DOIs
StatePublished - Nov 30 2007

Keywords

  • MOLIMMUNO
  • RNA
  • SIGNALING

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    Wan, F., Anderson, D. E., Barnitz, R. A., Snow, A., Bidere, N., Zheng, L., Hegde, V., Lam, L. T., Staudt, L. M., Levens, D., Deutsch, W. A., & Lenardo, M. J. (2007). Ribosomal Protein S3: A KH Domain Subunit in NF-κB Complexes that Mediates Selective Gene Regulation. Cell, 131(5), 927-939. https://doi.org/10.1016/j.cell.2007.10.009