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Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development
Lund University.
Lund University.
University of Pennsylvania.
Lund University.
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2005 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 106, no 6, 1995-2001 p.Article in journal (Refereed) Published
Abstract [en]

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 Notchs 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.

Place, publisher, year, edition, pages
American Society of Hematology , 2005. Vol. 106, no 6, 1995-2001 p.
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Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-74451DOI: 10.1182/blood-2004-12-4744ISI: 000231817400026OAI: oai:DiVA.org:liu-74451DiVA: diva2:484805
Available from: 2012-01-27 Created: 2012-01-27 Last updated: 2017-12-08

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Sigvardsson, Mikael

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