Abstract
CD25, the alpha chain of the interleukin-2 receptor, is expressed in activated T cells and has a significant role in autoimmune disease and tumorigenesis; however, the mechanisms regulating transcription of CD25 remain elusive. Here we identify the Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel non-Rel component in the nuclear factor-kappaB (NF-κB) complex that confers CD25 transcription. Our results demonstrate that Sam68 has an essential role in the induction and maintenance of CD25 in T cells. T-cell receptor engagement triggers translocation of the inhibitor of NF-κB kinase alpha (IKKα) from the cytoplasm to the nucleus, where it phosphorylates Sam68, causing complex formation with NF-κB in the nucleus. These findings reveal the important roles of KH domain-containing components and their spatial interactions with IKKs in determining the binding targets of NF-κB complexes, thus shedding novel insights into the regulatory specificity of NF-κB.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Base Sequence
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Binding Sites
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Cell Nucleus / metabolism
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DNA / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Gene Knockdown Techniques
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HEK293 Cells
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Humans
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I-kappa B Kinase / metabolism
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Interleukin-2 Receptor alpha Subunit / genetics
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Interleukin-2 Receptor alpha Subunit / metabolism*
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Jurkat Cells
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Lymphocyte Activation / immunology*
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Molecular Sequence Data
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NF-kappa B / metabolism*
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Phosphorylation
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Promoter Regions, Genetic / genetics*
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Protein Binding
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Protein Structure, Tertiary
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / metabolism*
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Receptors, Antigen, T-Cell / metabolism
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Ribosomal Proteins / metabolism
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Signal Transduction / genetics
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T-Lymphocytes / metabolism*
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Transcription Factor RelA / metabolism
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Transcription, Genetic
Substances
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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IL2RA protein, human
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Interleukin-2 Receptor alpha Subunit
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KHDRBS1 protein, human
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NF-kappa B
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RNA-Binding Proteins
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RPS3 protein, human
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Receptors, Antigen, T-Cell
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Ribosomal Proteins
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Transcription Factor RelA
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DNA
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I-kappa B Kinase