Kathrein Katie L, Chari Sheila, Winandy Susan
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
J Biol Chem. 2008 Apr 18;283(16):10476-84. doi: 10.1074/jbc.M709643200. Epub 2008 Feb 20.
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-Jkappa, allowing for cross-talk 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.
Ikaros和Notch1这两种基因转录调节因子在T细胞发育的许多阶段都至关重要。Ikaros和Notch活性的失调共同促进T细胞白血病的发生，这表明它们在发育中的T细胞的汇聚途径中发挥作用。在本报告中，描述了Ikaros与Notch协同作用的机制，揭示了Ikaros在调节白血病T细胞系中Notch靶基因Hes1表达方面的非冗余作用。我们提供的证据表明，Ikaros与转录抑制因子RBP-Jkappa协同直接抑制Hes1，从而实现Notch和Ikaros之间的相互作用，影响CD4表达的调节。综上所述，这些数据描述了Ikaros在T细胞发育过程中发挥功能的潜在机制，并将Ikaros定义为Hes1的专职抑制因子。
