Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation.
NF-kappaB 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-kappaB to specific gene regulatory sites, we used NF-kappaB 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-kappaB-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-kappaB bound to specific regulatory sites in chromatin. Thus, RPS3 is an essential but previously unknown subunit of NF-kappaB involved in the regulation of key genes in rapid cellular activation responses. Our observations provide insight into how NF-kappaB selectively controls gene expression.
Wan
Fengyi
F
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Anderson
D Eric
DE
Barnitz
Robert A
RA
Snow
Andrew
A
Bidere
Nicolas
N
Zheng
Lixin
L
Hegde
Vijay
V
Lam
Lloyd T
LT
Staudt
Louis M
LM
Levens
David
D
Deutsch
Walter A
WA
Lenardo
Michael J
MJ
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity
D002843:Chromatin; D046912:Multiprotein Complexes; D016328:NF-kappa B; D021122:Protein Subunits; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; C044152:ribosomal protein S3