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

• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0603728103

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.