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 journalArticlepeer-review

231 Scopus citations


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 (US)
Pages (from-to)927-939
Number of pages13
Issue number5
StatePublished - Nov 30 2007
Externally publishedYes


  • RNA

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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