Abstract
CD7, one of the galectin-1 receptors, has crucial roles in galectin-1-mediated apoptosis of activated T-cells and T-lymphoma progression in peripheral tissues. In this study, we showed that CD7 promoter activity was increased by NF-kappaB and that this activity was synergistic when Sp1 was co-expressed in the immature T-cell line L7. Site-directed mutagenesis analysis of the CD7 promoter indicated that NF-kappaB specifically bound to the NF-kappaE2 site in cooperation with Sp1. Overexpression of E12 or Twist2 proteins negatively regulated NF-kappaB-mediated activity of the CD7 proximal promoter. In addition, CD7 expression was down-regulated by treatment with the p38 MAPK inhibitor SB20358, or the MSK1 inhibitor H-89. These signaling pathway inhibitors prevented galectin-1-mediated apoptosis of immature T-cells. From these results, we concluded that the regulation of CD7 gene expression through NF-kappaB activation induced by TCR/CD28 might have significant implications for T-cell homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD7 / genetics*
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Apoptosis*
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Down-Regulation
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Galectin 1 / metabolism*
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Galectin 1 / pharmacology
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Gene Expression Regulation, Developmental*
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Lymphocyte Activation
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Mice
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NF-kappa B / metabolism*
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Promoter Regions, Genetic / drug effects
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Repressor Proteins / metabolism
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Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism
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Sp1 Transcription Factor / metabolism
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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TCF Transcription Factors / metabolism
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Transcription Factor 7-Like 1 Protein
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Twist-Related Protein 1 / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Antigens, CD7
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Galectin 1
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NF-kappa B
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Repressor Proteins
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Sp1 Transcription Factor
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TCF Transcription Factors
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Twist-Related Protein 1
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Twist2 protein, mouse
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Ribosomal Protein S6 Kinases, 90-kDa
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mitogen and stress-activated protein kinase 1
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p38 Mitogen-Activated Protein Kinases