| Pin1 is a novel peptidyl-prolyl isomerase that can specifically isomerize the phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) bond, and regulates the function of a defined subset of phosphoproteins. Axin, which plays a critical role in diverse biological processes, is a scaffold protein with multiple function domains. It binds to APC,β-catenin, GSK-3βand LRP5, serving as a negative regulator which promotes the degradation ofβ-catenin in Wnt signal pathway. In addition, Axin is also involved in the p53, JNK and TGF-βsignal pathways. However, it is still not well understood how Axin is regulated and how Axin is able to regulate such complex signal pathways. In this thesis we present the first evidence that Axin interacts with the peptidyl-prolyl isomerase Pin1 and the Axin-binding site of Pin1 locates at the WW domain. Though Pin1 does not influence the regulatory role of Axin in the Wnt signal pathway, Pin1 and Axin additively activate TGF-βsignaling. In addition, Pin1 and Axin synergically enhance the transcriptional activity of p53, indicating that Pin1 can selectively regulate the function of Axin. Our data shed new light on the mechanism of the Axin-mediated p53 activation.Futhermore, we studied the interaction between Pin1 and Daxx, a highly conserved, multi-functional protein. Despite a number of studies attempting to uncover the function of Daxx in apoptosis and growth, its precise role in these processes is still in controversy. Here we cloned human Daxx gene and showed that Daxx interacted and co-localized with Pin1. This founding implicated the Pin1's role in the regulation of Daxx-modulated cell death and provided a potential approach to the understanding of the function of Daxx.
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