RESUMO
Leukocyte associated Ig-like receptor-1 (LAIR-1) is a surface molecule expressed on human mononuclear leukocytes that functions as an inhibitory receptor on human NK cells. In addition to NK cells, LAIR-1 is expressed on T cells, B cells, macrophages, and dendritic cells. Most cells express two biochemically distinct forms of LAIR-1, which we now show are likely alternative splice variants of the same gene. Cross-linking of LAIR-1 on human T cell clones results in inhibition of cytotoxicity only in T cell clones that lack CD28 and are able to spontaneously lyse certain targets in vitro. Moreover, the cytolytic activity of freshly isolated T cells, which is thought to be mainly due to "effector" T cells, can be inhibited by anti-LAIR-1 mAb. Thus, LAIR-1 functions as an inhibitory receptor not only on NK cells, but also on human T cells. This indicates that LAIR-1 provides a mechanism of regulation of effector T cells and may play a role in the inhibition of unwanted bystander responses mediated by Ag-specific T cells.
Assuntos
Células Matadoras Naturais/imunologia , Receptores Imunológicos/imunologia , Linfócitos T Citotóxicos/imunologia , Processamento Alternativo , Sequência de Aminoácidos , Antígenos CD28/imunologia , Células Clonais , Citotoxicidade Imunológica , Humanos , Células Jurkat , Dados de Sequência Molecular , Receptores Imunológicos/genética , Homologia de Sequência de AminoácidosRESUMO
We have recently identified the HMG box transcription factor Sox-13 and described its expression during murine embryogenesis. Here we describe the structure of the murine Sox-13 gene. This gene spans approximately 12 kb and consists of 13 exons. The HMG domain is encoded by exons XI and XII, separated by an intron that is conserved among Sox-5, Sox-13, and Sox-17. A single major transcription initiation site was identified. Deletion analysis of the 3-kb promoter region revealed a 400-bp fragment driving transcription of a luciferase reporter in a Sox-13-expressing cell line. To determine the chromosomal localization of the human gene, a human SOX13 cDNA was isolated with 75% homology to the mouse Sox-13. FISH analysis mapped the human SOX13 gene to chromosome 1 band q32.
Assuntos
Autoantígenos , Proteínas de Grupo de Alta Mobilidade/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 1/genética , DNA/química , DNA/genética , Éxons , Regulação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Íntrons , Luciferases/genética , Luciferases/metabolismo , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , RNA/genética , RNA/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Transcrição SOXD , Análise de Sequência de DNA , Distribuição TecidualRESUMO
Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by recruiting Armadillo/beta-catenin as a transcriptional co-activator. However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors. Here we show that Tcf factors physically interact with members of the Groucho family of transcriptional repressors. In transient transfection assays, the Xenopus Groucho homologue XGrg-4 inhibited activation of transcription of synthetic Tcf reporter genes. In contrast, the naturally truncated Groucho-family member XGrg-5 enhanced transcriptional activation. Injection of XGrg-4 into Xenopus embryos repressed transcription of Siamois and Xnr-3, endogenous targets of beta-catenin-Tcf. Dorsal injection of XGrg-4 had a ventralizing effect on Xenopus embryos. Secondary-axis formation induced by a dominant-positive Armadillo-Tcf fusion protein was inhibited by XGrg-4 and enhanced by XGrg-5. These data indicate that expression of Tcf target genes is regulated by a balance between Armadillo and Groucho.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila , Proteínas HMGB , Proteínas Repressoras/metabolismo , Transativadores , Fatores de Transcrição/metabolismo , Animais , Proteínas do Domínio Armadillo , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células COS , Clonagem Molecular , Proteínas de Insetos/metabolismo , Dados de Sequência Molecular , Proteínas/genética , Fatores de Transcrição TCF , Fator 3 de Transcrição , Proteína 1 Semelhante ao Fator 7 de Transcrição , Xenopus , Proteínas de XenopusRESUMO
Approximately 25-30% of childhood pre-B cell acute lymphoblastic leukemias (pre-B ALL) is characterized by the presence of a (1;19)(q23;p13.3) translocation. The presence of this translocation is generally accompanied by a poor prognosis. The chimeric gene resulting from this chromosomal rearrangement encodes a hybrid transcription factor, E2A-Pbx1. In an attempt to delineate the genetic cascade initiated by E2A-Pbx1, we sought to identify genes that are deregulated by this transcription factor in t(1;19) pre-B ALL. We show here that the gene encoding the granulocyte colony-stimulating factor receptor (G-CSFr) is specifically upregulated in pre-B cells expressing E2A-Pbx1. G-CSFr is also expressed in cell lines established from t(1;19) pre-B cell leukemia and on primary t(1;19) tumor cells, but not on control cells. These data indicate that G-CSFr gene is a target for deregulation by E2A-Pbx1.
