Title: The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1 activation in cancer
Authors: Rustighi, Alessandra *
Tiberi, Luca *
Soldano, Alessia
Napoli, Marco
Nuciforo, Paolo
Rosato, Antonio
Kaplan, Fred
Capobianco, Anthony
Pece, Salvatore
Di Fiore, Pier Paolo
Del Sal, Giannino # ×
Issue Date: Feb-2009
Publisher: Macmillan Magazines Ltd.
Series Title: Nature Cell Biology vol:11 issue:2 pages:133-42
Abstract: Signalling through Notch receptors requires ligand-induced cleavage to release the intracellular domain, which acts as a transcriptional activator in the nucleus. Deregulated Notch1 signalling has been implicated in mammary tumorigenesis; however the mechanisms underlying Notch activation in breast cancer remain unclear. Here, we demonstrate that the prolyl-isomerase Pin1 interacts with Notch1 and affects Notch1 activation. Pin1 potentiates Notch1 cleavage by gamma-secretase, leading to an increased release of the active intracellular domain and ultimately enhancing Notch1 transcriptional and tumorigenic activity. We found that Notch1 directly induces transcription of Pin1, thereby generating a positive loop. In human breast cancers, we observed a strong correlation between Pin1 overexpression and high levels of activated Notch1. Thus, the molecular circuitry established by Notch1 and Pin1 may have a key role in cancer.
ISSN: 1465-7392
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
* (joint) first author
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1 activation in cancer..pdfMain article Published 1905KbAdobe PDFView/Open


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science