TY - JOUR
T1 - The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1 activation in cancer
AU - Rustighi, Alessandra
AU - Tiberi, Luca
AU - Soldano, Alessia
AU - Napoli, Marco
AU - Nuciforo, Paolo
AU - Rosato, Antonio
AU - Kaplan, Fred
AU - Capobianco, Anthony
AU - Pece, Salvatore
AU - Di Fiore, Pier Paolo
AU - Del Sal, Giannino
PY - 2009
Y1 - 2009
N2 - 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 γ-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.
AB - 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 γ-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.
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U2 - 10.1038/ncb1822
DO - 10.1038/ncb1822
M3 - Article
C2 - 19151708
AN - SCOPUS:59649106779
VL - 11
SP - 133
EP - 142
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 2
ER -