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

• Published in: Cell Vol. 131; no. 5; pp. 927 - 939
• Main Authors: Wan, F, Anderson, DE, Barnitz, R A, Snow, A, Bidere, N, Zheng, L, Hegde, V, Lam, L T, Staudt, L M, Levens, D, Deutsch, WA, Lenardo, MJ
• Format: Journal Article
• Language: English
• Published: 30.11.2007
• ISSN: 0092-8674
• DOI: 10.1016/j.cell.2007.10.009

NF- Kappa B 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- Kappa B to specific gene regulatory sites, we used NF- Kappa B 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- Kappa B-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- Kappa B bound to specific regulatory sites in chromatin. Thus, RPS3 is an essential but previously unknown subunit of NF- Kappa B involved in the regulation of key genes in rapid cellular activation responses. Our observations provide insight into how NF- Kappa B selectively controls gene expression.