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Molecular and Cellular Biology, November 2001, p. 7537-7544, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7537-7544.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Notch Intracellular Domain Can Function as a Coactivator for LEF-1

David A. Ross and Tom Kadesch*

Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6145

Received 24 May 2001/Returned for modification 13 July 2001/Accepted 8 August 2001

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.

* Corresponding author. Mailing address: Department of Genetics, University of Pennsylvania School of Medicine, 409 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104-6145. Phone: (215) 898-1047. Fax: (215) 898-9750. E-mail: kadesch{at}mail.med.upenn.edu.

Molecular and Cellular Biology, November 2001, p. 7537-7544, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7537-7544.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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