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

Smith, Emma LU ; Akerblad, P; Kadesch, T; Axelson, Håkan LU and Sigvardsson, Mikael LU (2005) In Blood 106(6). p.1995-2001
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
106
issue
6
pages
1995 - 2001
publisher
American Society of Hematology
external identifiers
  • pmid:15920012
  • wos:000231817400026
  • scopus:24744442149
ISSN
1528-0020
DOI
10.1182/blood-2004-12-4744
language
English
LU publication?
yes
id
3d954f21-7901-4f3b-a44f-86fcd0a18cfb (old id 225098)
date added to LUP
2007-08-15 15:50:02
date last changed
2017-02-26 03:35:38
@article{3d954f21-7901-4f3b-a44f-86fcd0a18cfb,
  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.},
  author       = {Smith, Emma and Akerblad, P and Kadesch, T and Axelson, Håkan and Sigvardsson, Mikael},
  issn         = {1528-0020},
  language     = {eng},
  number       = {6},
  pages        = {1995--2001},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development},
  url          = {http://dx.doi.org/10.1182/blood-2004-12-4744},
  volume       = {106},
  year         = {2005},
}