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 language | English (US) |
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Pages (from-to) | 927-939 |
Number of pages | 13 |
Journal | Cell |
Volume | 131 |
Issue number | 5 |
DOIs | |
State | Published - Nov 30 2007 |
Externally published | Yes |
Keywords
- MOLIMMUNO
- RNA
- SIGNALING
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology