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 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.
Schwartz
Ruth
R
Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0377, USA.
Engel
Isaac
I
Fallahi-Sichani
Mohammad
M
Petrie
Howard T
HT
Murre
Cornelis
C
D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053613:Janus Kinase 1; D050356:Lipid Metabolism / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000502:physiology*; D058125:Transcription Factor 7-Like 1 Protein
D016207:Cytokines; D015375:Receptors, Interleukin-2; D050826:Suppressor of Cytokine Signaling Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D058125:Transcription Factor 7-Like 1 Protein; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1