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 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Schwartz R,Engel I,Fallahi-Sichani M,Petrie HT,Murre Cdoi
10.1073/pnas.0603728103subject
Has Abstractpub_date
2006-06-27 00:00:00pages
9976-81issue
26eissn
0027-8424issn
1091-6490pii
0603728103journal_volume
103pub_type
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