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PMID: 11604490 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The notch intracellular domain can function as a coactivator for LEF-1.

Molecular and cellular biology ·Vol. 21 ·No. 22 ·2001-11-00 ·Pages 7537-44

Ross DA, Kadesch T

Abstract

Notch signaling commences with two ligand-mediated proteolysis events that release the Notch intracellular domain, NICD, from the plasma membrane. NICD then translocates into the nucleus and interacts with the DNA binding protein CSL to activate transcription. We found that NICD expression also potentiates activity of the transcription factor LEF-1. NICD stimulation of LEF-1 activity was context dependent and occurred on a subset of promoters distinct from those activated by beta-catenin. Importantly, the effect of NICD does not appear to be mediated through canonical components of the Wnt signaling pathway or downstream components of the Notch pathway. In vitro assays show a weak association between the C-terminal transactivation domain of NICD and the high-mobility group domain of LEF-1, suggesting that the two proteins interact in vivo. Our data therefore describe a new nuclear target of Notch signaling and a new coactivator for LEF-1.

MeSH Terms
Animals Binding Sites Cell Line DNA-Binding Proteins/genetics,metabolism Humans Intracellular Fluid Jurkat Cells Lymphoid Enhancer-Binding Factor 1 Membrane Proteins/genetics,metabolism,physiology Proto-Oncogene Proteins/metabolism Receptors, Notch Trans-Activators/genetics,metabolism,physiology Transcription Factors/genetics,metabolism Transcriptional Activation Wnt Proteins Zebrafish Proteins
Chemicals
DNA-Binding Proteins LEF1 protein, human Lymphoid Enhancer-Binding Factor 1 Membrane Proteins Proto-Oncogene Proteins Receptors, Notch Trans-Activators Transcription Factors Wnt Proteins Zebrafish Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ross D A
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, 19104-6145, USA.
Kadesch T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.22.7537-7544.2001
Published
2001-11-00
Pages
7537-44
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC99925
Subset
IM
Grants
NCI NIH HHS · T32 CA009140 · United States
NIGMS NIH HHS · R01 GM58228 · United States
NCI NIH HHS · T32 CA09140 · United States
External Links
PubMed source DOI: 10.1128/MCB.21.22.7537-7544.2001 PMC Full Text View journal details
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