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- Title
Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1.
- Authors
Wulf, Gerburg M.; Ryo, Akihide; Wulf, Gerald G.; Lee, Sam W.; Niu, Tianhua; Petkova, Victoria; Kun Ping Lu
- Abstract
Phosphorylation on serines or threonines preceding proline (Ser/Thr-Pro) is a major signaling mechanism. The conformation of a subset of phosphorylated Sen Thr-Pro motifs is regulated by the protyl isomerase Pin1. Inhibition of Pin1 induces apoptosis and may also contribute to neuronal death in Atzheimer's disease. However, little is known about the rote of Pin1 in cancer or in modulating transcription factor activity. Here we report that Pin1 is strikingly overexpressed in human breast cancers, and that its levels correlate with cyclin D1 levels in tumors. Overexpression of Pin1 increases cellular cyclin D1 protein and activates its promoter. Furthermore, Pin1 binds c-Jun that is phosphorylated on Ser63/73-Pro motifs by activated JNK or oncogenic Ras. Moreover, Pin1 cooperates with either activated Ras or JNK to increase transcriptional activity of c-Jun towards the cyctin D1 promoter. Thus, Pin1 is up-regulated in human tumors and cooperates with Ras signaling in increasing c-Jun transcriptional activity towards cyclin D1. Given the crucial roles of Ras signaling and cyclin D1 overexpression in oncogenesis, our results suggest that overexpression of Pin1 may promote tumor growth.
- Subjects
BREAST cancer; TRANSCRIPTION factors; CYCLINS; APOPTOSIS; TUMORS; ONCOLOGY
- Publication
EMBO Journal, 2001, Vol 20, Issue 13, p3459
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/20.13.3459