Gene Expression Patterns Define Novel Roles for E47 in Cell Cycle Progression, Cytokine-Mediated Signaling, and T Lineage Development

In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cel...

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Published in	Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 26; pp. 9976 - 9981
Main Authors	Schwartz, Ruth, Engel, Isaac, Fallahi-Sichani, Mohammad, Petrie, Howard T., Murre, Cornelis
Format	Journal Article
Language	English
Published	United States National Academy of Sciences 27.06.2006 National Acad Sciences
Subjects	Biological Sciences Cell cycle Cell Cycle - genetics Cell Line, Tumor Cell Lineage - genetics Cell lines Cell Proliferation Cell Survival - genetics Cytokines Cytokines - metabolism Developmental biology Gene expression Gene expression regulation Gene Expression Regulation, Neoplastic Genes Humans Janus Kinase 1 Lipid Metabolism - genetics Lymphoma Lymphoma - genetics Natural killer T cells Oligonucleotide Array Sequence Analysis Protein-Tyrosine Kinases - genetics Proteins Receptors, Interleukin-2 - genetics Signal Transduction Suppressor of Cytokine Signaling Proteins - genetics T lymphocytes T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - metabolism TCF Transcription Factors - genetics TCF Transcription Factors - physiology Thymocytes Transcription Factor 7-Like 1 Protein
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ISSN	0027-8424 1091-6490
DOI	10.1073/pnas.0603728103

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Abstract	In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcγ2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfil, Gfilb, Socsl, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy.
AbstractList	In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as beta selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcgamma2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy.In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as beta selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcgamma2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. In maturing T lineage cells, the helix–loop–helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcγ2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as beta selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcgamma2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as beta selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plc gamma 2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcγ2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfil, Gfilb, Socsl, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. In maturing T lineage cells, the helix–loop–helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as β selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcγ2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, Id2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. E2A Gfi SOCS Xbp1 In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as ß selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA microarray analysis to identify immediate E47 target genes. Hierarchical cluster analysis of gene expression patterns revealed that E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. These include Plcγ2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, Socs3, ld2, Eto2, and Xbp1. We propose a regulatory network linking Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated signaling, E47, and suppressor of cytokine signaling (SOCS) proteins in a common pathway. Finally, we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the development of lymphoid malignancy. [PUBLICATION ABSTRACT]
Author	Petrie, Howard T. Engel, Isaac Schwartz, Ruth Fallahi-Sichani, Mohammad Murre, Cornelis
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/16782810$$D View this record in MEDLINE/PubMed
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Notes	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 Communicated by Michael S. Levine, University of California, Berkeley, CA, May 5, 2006 Author contributions: R.S., I.E., and C.M. designed research; R.S., I.E., and M.F.-S. performed research; R.S., I.E., M.F.-S., H.T.P., and C.M. analyzed data; and C.M. wrote the paper. Present address: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92122. R.S. and I.E. contributed equally to this work.
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Snippet	In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred... In maturing T lineage cells, the helix–loop–helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred...
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SubjectTerms	Biological Sciences Cell cycle Cell Cycle - genetics Cell Line, Tumor Cell Lineage - genetics Cell lines Cell Proliferation Cell Survival - genetics Cytokines Cytokines - metabolism Developmental biology Gene expression Gene expression regulation Gene Expression Regulation, Neoplastic Genes Humans Janus Kinase 1 Lipid Metabolism - genetics Lymphoma Lymphoma - genetics Natural killer T cells Oligonucleotide Array Sequence Analysis Protein-Tyrosine Kinases - genetics Proteins Receptors, Interleukin-2 - genetics Signal Transduction Suppressor of Cytokine Signaling Proteins - genetics T lymphocytes T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - metabolism TCF Transcription Factors - genetics TCF Transcription Factors - physiology Thymocytes Transcription Factor 7-Like 1 Protein
Title	Gene Expression Patterns Define Novel Roles for E47 in Cell Cycle Progression, Cytokine-Mediated Signaling, and T Lineage Development
URI	https://www.jstor.org/stable/30051026 http://www.pnas.org/content/103/26/9976.abstract https://www.ncbi.nlm.nih.gov/pubmed/16782810 https://www.proquest.com/docview/201386518 https://www.proquest.com/docview/17264253 https://www.proquest.com/docview/68572235 https://pubmed.ncbi.nlm.nih.gov/PMC1502564
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