Prolyl Isomerase Pin1 in Phosphorylation Signaling, Aging and Cancer

Phosphorylation of proteins on serine or threonine residues preceding proline is a key signaling mechanism in diverse physiological and pathological processes. Pin1 is the only enzyme known so far that can isomerize specific Ser/Thr-Pro peptide bonds after phosphorylation and promote their conformational changes with high efficiency. These Pin1-induced conformational changes upon phosphorylation can have profound effects on phosphorylation signaling by regulating a spectrum of target activities. Interestingly, Pin1 deregulation is implicated in an increasing number of diseases, notably aging and age-related disease including cancer and Alzheimer’s disease. Pin1 is overexpressed in most human cancers, and activates numerous oncogenes or growth enhancers and also inactivates a large number of tumor suppressors or growth inhibitors. In contrast, Pin1 ablation prevents cancer development, but leads to premature aging and neurodegeneration. Therefore, Pin1-mediated phosphorylation-dependent prolyl isomerization represents a novel and unique signaling mechanism that plays a pivotal role in the development of human diseases, and might offer an attractive new diagnostic and therapeutic target. Thus this talk will be focused on the role of Pin1 in aging and age-related diseases, and discuss its translational applications for new disease diagnosis and therapeutic interventions.