Defective activation and survival of T cells lacking the Ets-1 transcription factor

THE Ets-1 proto-oncogene 1 is a member of the Ets family of eukaryotic transcription factors 2á¤-7 . Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals 4,5,8,9 . Ets-1 is preferentially expressed at high levels in B a...

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Published in:Nature (London) 1995-10, Vol.377 (6550), p.639-642
Main Authors: Muthusamy, Natarajan, Barton, Kevin, Leiden, Jeffrey M.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Biological and medical sciences
CD3 Complex - biosynthesis
CD4 Antigens - biosynthesis
CD8 Antigens - biosynthesis
Cell Division - physiology
Cell Line
Cell Survival - physiology
Cellular biology
Chimera
DNA-Binding Proteins
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genes
Humanities and Social Sciences
Immunobiology
letter
Lymphocyte Activation - physiology
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Mice
multidisciplinary
Mutation
Proteins - physiology
Proto-Oncogene Protein c-ets-1
Proto-Oncogene Proteins - deficiency
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-ets
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Science
Science (multidisciplinary)
Sequence Deletion
Spleen - cytology
Stem Cells
T-Lymphocytes - immunology
T-Lymphocytes - physiology
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - physiology
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description THE Ets-1 proto-oncogene 1 is a member of the Ets family of eukaryotic transcription factors 2á¤-7 . Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals 4,5,8,9 . Ets-1 is preferentially expressed at high levels in B and T cells of adult mice 10,11 and is regulated during both thymocyte development 11 and T-cell activation *12, 13 . To study the role of Ets-1 in T-cell development and function we have used the RAG-2 -/- complementation system 14 and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene ( Ets-1 -/- ). Ets-1 -/- - RAG-2 -/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1 -/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-α/β. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro . These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.
doi_str_mv 10.1038/377639a0
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Psychology ; Fundamental immunology ; Genes ; Humanities and Social Sciences ; Immunobiology ; letter ; Lymphocyte Activation - physiology ; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation ; Mice ; multidisciplinary ; Mutation ; Proteins - physiology ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins - deficiency ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - physiology ; Proto-Oncogene Proteins c-ets ; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis ; Science ; Science (multidisciplinary) ; Sequence Deletion ; Spleen - cytology ; Stem Cells ; T-Lymphocytes - immunology ; T-Lymphocytes - physiology ; Transcription Factors - deficiency ; Transcription Factors - genetics ; Transcription Factors - physiology</subject><ispartof>Nature (London), 1995-10, Vol.377 (6550), p.639-642</ispartof><rights>Springer Nature Limited 1995</rights><rights>1995 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. 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Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals 4,5,8,9 . Ets-1 is preferentially expressed at high levels in B and T cells of adult mice 10,11 and is regulated during both thymocyte development 11 and T-cell activation *12, 13 . To study the role of Ets-1 in T-cell development and function we have used the RAG-2 -/- complementation system 14 and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene ( Ets-1 -/- ). Ets-1 -/- - RAG-2 -/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1 -/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-α/β. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro . These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>7566177</pmid><doi>10.1038/377639a0</doi><tpages>4</tpages></addata></record>
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subjects Animals
Apoptosis - physiology
Biological and medical sciences
CD3 Complex - biosynthesis
CD4 Antigens - biosynthesis
CD8 Antigens - biosynthesis
Cell Division - physiology
Cell Line
Cell Survival - physiology
Cellular biology
Chimera
DNA-Binding Proteins
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genes
Humanities and Social Sciences
Immunobiology
letter
Lymphocyte Activation - physiology
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Mice
multidisciplinary
Mutation
Proteins - physiology
Proto-Oncogene Protein c-ets-1
Proto-Oncogene Proteins - deficiency
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-ets
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Science
Science (multidisciplinary)
Sequence Deletion
Spleen - cytology
Stem Cells
T-Lymphocytes - immunology
T-Lymphocytes - physiology
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - physiology
title Defective activation and survival of T cells lacking the Ets-1 transcription factor
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