Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development

Emma Smith, P Akerblad, T Kadesch, Håkan Axelson, Mikael Sigvardsson

Research output: Contribution to journalArticlepeer-review

50 Citations (SciVal)

Abstract

The Notch signaling pathway is involved in several lineage commitment and differentiation events. One of these is fate determination of the common lymphoid progenitor, promoting T-cell development at the expense of B-cell differentiation. It has been suggested that this process relies on Notch's ability to inhibit E proteins, which are crucial for early B-cell development. Here, we report that Notch signaling also modulates the function of the transcription factor, early B-cell factor (EBF). Transient transfection of intracellular Notch1 (Notch1-IC) into a pre-B cell line resulted in the down-regulation of EBF-regulated promoters and diminished the capacity of EBF to activate these promoters in an epithelial cell line. This correlated with a reduction in the ability of EBF to bind DNA. Ligand-induced stimulation of endogenous Notch receptors with Delta4 mimicked the activity of Notch1-IC toward EBF. These data suggest that Notch signaling may affect B- versus T-lineage commitment by the targeting of both EBF and E2A.
Original languageEnglish
Pages (from-to)1995-2001
JournalBlood
Volume106
Issue number6
DOIs
Publication statusPublished - 2005

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012), Molecular Tumour Biology (013017540)

Department affilation moved from v1000583 (Molecular Tumour Biology) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:41:48.

Subject classification (UKÄ)

  • Hematology

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