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The central role of Pin1 in age-related cancer signaling pathways
George Xie1, Sho Okuda1, Jing-Yan Gao2
1Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada.
Abstract:
The prolyl-isomerase Pin1 is a unique enzyme that catalyzes cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs. These motifs are present in many proteins, where isomerization of the typically rigid prolyl-peptide bond can lead to conformational changes, and subsequently regulate activity, stability, or localization. The specificity of Pin1 for phosphorylated motifs allows it to serve as a master regulator of proteins after phosphorylation, adding an additional layer of regulation to intricately control cellular signaling. As such, Pin1 plays an expansive role in numerous cancer and age-related signaling pathways, and is recognized as a major driver of cancer and promising therapeutic target. In this review, we discuss the role of Pin1 in regulation of age-related cancer signaling pathways, and we highlight the early development and current landscape of Pin1 inhibitors, and the prospect of Pin1 inhibition for cancer therapy.
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