title: Sam68 modulates the promoter specificity of NF-κB and mediates expression of CD25 in activated T cells.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21025, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wier
authors.forename: Andrea
authors.initials: A
authors.lastname: Hodgson
authors.forename: Dat Q
authors.initials: DQ
authors.lastname: Tran
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
authors.forename: Fengyi
authors.initials: F
authors.lastname: Wan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C489559:KHDRBS1 protein, human; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C578290:RPS3 protein, human; D011948:Receptors, Antigen, T-Cell; D012269:Ribosomal Proteins; D051996:Transcription Factor RelA; D004247:DNA; D051550:I-kappa B Kinase