title: Blimp-1/PRDM1 regulates the transcription of human CS1 (SLAMF7) gene in NK and B cells.
abstract: CS1 (CRACC/CD319/SLAMF7) is a member of SLAM (Signaling Lymphocyte Activation Molecule) family receptors and is expressed on NK cells, a subset of CD8(+) T lymphocytes, activated monocytes, mature dendritic cells and activated B cells. In NK cells, CS1 signaling induces cytolytic function of NK cells against targets whereas in B cells CS1 induces proliferation and autocrine cytokine production. CS1 is upregulated in multiple myeloma cells and contributes to clonogenic growth and tumorigenicity. However, the mechanism of CS1 upregulation is unknown. In this study, we analyzed the transcriptional regulation of human CS1 gene in NK and B cells. The promoter region of CS1 contains a Blimp-1/PRDM1 binding site and relative luciferase activities of successive deletion mutants of CS1 promoter were different between Blimp-1/PRDM1-positive and Blimp-1/PRDM1-negative cells. Proximal region of CS1 promoter contains a CAAT box and atypical TATA-box that might result in common transcription initiation at -29 nucleotides upstream of the ATG translation start codon. Electrophoretic Mobility Shift Assay (EMSA) and Chromatin Immunoprecipitation (ChIP) assays revealed Blimp-1/PRDM1 binds to the CS1 promoter region. Mutating the Blimp-1/PRDM1 site at -750 to -746 decreased the transcriptional activity of CS1 promoter implicating a trans-activating function of Blimp-1/PRDM1 in human CS1 gene regulation. The finding that Blimp-1/PRDM1 enhances transcription of CS1 gene in multiple myeloma cells may help in developing novel strategies for therapeutic intervention in multiple myeloma.
authors: Department of Cell Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.
authors: Jong R
authors: JR
authors: Kim
authors: Department of Cell Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.
authors: Stephen O
authors: SO
authors: Mathew
authors: Department of Cell Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA. Electronic address: Porunelloor.mathew@unthsc.edu.
authors: Porunelloor A
authors: PA
authors: Mathew
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family; D014158:Transcription, Genetic
chemical_list: D011971:Receptors, Immunologic; D012097:Repressor Proteins; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; C087042:PRDM1 protein, human; D008156:Luciferases; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: B cells; Blimp-1/PRDM1; CS1; NK cells