Research ArticleImmunology

The Tumor Suppressor Ikaros Shapes the Repertoire of Notch Target Genes in T Cells

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Science Signaling  18 Mar 2014:
Vol. 7, Issue 317, pp. ra28
DOI: 10.1126/scisignal.2004545

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Another Notch in Ikaros’ Belt

Signaling by the Notch family of receptors is required for the early stages of thymocyte differentiation into T cells, after which the expression of Notch target genes is silenced. Aberrant Notch signaling in mature thymocytes and T cells causes T cell acute lymphoblastic leukemia/lymphoma (T-ALL). Geimer Le Lay et al. performed genome-wide analyses of Notch target genes in T cells and found that the tumor suppressor protein Ikaros was recruited to sites adjacent to those bound by the Notch transcriptional coregulator RBPJ. Recruitment of Ikaros repressed the expression of most Notch target genes. Thymocytes from Ikaros mutant mice exhibited aberrant expression of Notch target genes at the later stages of development and developed T-ALL. Together, these data suggest that the appropriate expression of most Notch target genes is dependent on the repressive effect of Ikaros.

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