Fig. 2. Pin1 functions as a critical catalyst for integrating multiple oncogenic signaling pathways. Pin1 gene expression is induced by growth factor signaling through Neu and Ras signaling. Ras signaling induces JNK/SAPK activity to phosphorylate Jun. Subsequently, Pin1 binds to and isomerizes phosphorylated Jun to enhance its transcriptional activity. In parallel, Pin1 activates the ß-catenin pathway by preventing ß-catenin binding to APC, which can induce Jun gene expression. These signaling cascades eventually lead to an increase in cyclin D1 transcription. Furthermore, Pin1 also directly binds to and stabilizes cyclin D1 protein. In addition, Pin1 can induce the c-Myc gene through the activation of the ß-catenin pathway, which can then enhance cyclin D1 function by inducing Cdk4 gene expression and/or directly activate E2F family genes. Finally, E2F can induce Pin1 expression in a positive feedback loop involving the cyclin D1/E2F pathway.