Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development
Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development
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DOI：
10.1073/pnas.0603728103
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发表时间：
2006-06-27
影响因子：
11.1
通讯作者：
Murre, Cornelis
中科院分区：
文献类型：
--
作者：
Schwartz, Ruth;Engel, Isaac;Murre, Cornelis
在成熟的 T 谱系细胞中，螺旋-环-螺旋蛋白 E47 已被证明可以执行一个关键的增殖和发育检查点，通常称为 A 选择。为了研究 E47 如何调节细胞扩张和发育进程，我们使用 E2A 缺陷的淋巴瘤细胞系和 DNA 微阵列分析来识别直接 E47 靶基因。基因表达模式的层次聚类分析表明，E47 协调调节与细胞存活、细胞周期进程、脂质代谢、应激反应和淋巴成熟相关的基因的表达。这些包括 Plc gamma 2、Cdk6、CD25、Tox、Gadd45a、Gadd45b、Gfi1、Gfi1b、Socs1、Socs3、Id2、Eto2 和 Xbp1。我们提出了一个调节网络，将 Janus 激酶 (JAK)/信号转导器和转录激活剂 (STAT) 介导的信号传导、E47 和细胞因子信号传导抑制蛋白 (SOCS) 蛋白连接在一个共同途径中。最后，我们认为 E47 缺陷的 T 谱系细胞中 Cdk6 的异常激活有助于淋巴恶性肿瘤的发生。
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 A 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.