Ikaros directly represses the notch target gene Hes1 in a leukemia T cell line -: Implications for CD4 regulation
Ikaros directly represses the notch target gene Hes1 in a leukemia T cell line -: Implications for CD4 regulation
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DOI：
10.1074/jbc.m709643200
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发表时间：
2008-04-18
影响因子：
4.8
通讯作者：
Winandy, Susan
中科院分区：
文献类型：
--
作者：
Kathrein, Katie L.;Chari, Sheila;Winandy, Susan
Ikaros和Notch 1是基因转录的两个调节因子，在T细胞发育的许多阶段都至关重要。Ikaros和Notch活性的失调协同促进T细胞白血病发生，提供了它们在发育中的T细胞的会聚途径中起作用的证据。在这份报告中，Ikaros的机制：Notch的协同作用进行了描述，揭示了非冗余的作用，Ikaros在调节表达的Notch靶基因Hes 1在白血病T细胞系。我们提供的证据表明，Ikaros与转录抑制因子RBP-J kappa一起直接抑制Hes 1，从而允许Notch和Ikaros之间的串扰影响CD 4表达的调节。总之，这些数据描述了Ikaros在T细胞发育过程中功能的潜在机制，并将Ikaros定义为Hes 1的专性阻遏物。
Ikaros and Notch1, two regulators of gene transcription, are critically important at many stages of T cell development. Deregulation of Ikaros and Notch activities cooperate to promote T cell leukemogenesis, providing evidence that they function in converging pathways in developing T cells. In this report, a mechanism for Ikaros: Notch cooperativity is described, revealing a non-redundant role for Ikaros in regulating expression of the Notch target gene Hes1 in a leukemia T cell line. We provide evidence that Ikaros directly represses Hes1 in concert with the transcriptional repressor, RBP-J kappa, allowing for crosstalk between Notch and Ikaros that impacts regulation of CD4 expression. Taken together, these data describe a potential mechanism for Ikaros' function during T cell development and define Ikaros as an obligate repressor of Hes1.