Editorial: Phosphorylation-Dependent Peptidyl-Prolyl Cis/Trans Isomerase PIN1

摘要

PIN1 has been known to isomerize the phosphorylated serine/threonine-proline (pS/pT-P) motif and exert its physiological function by regulating multiple phosphorylated signaling proteins via different mechanisms for one ultimate goal of the cell, for instance osteogenic differentiation, an example not covered by the articles in this Research Topic. In particular, PIN1 regulates osteogenesis via stabilizing RUNX2 or OSX from ubiquitination, or by increasing nuclear retention of β-catenin in Wnt3a-induced osteoblast (Yoon et al., 2013; Lee et al., 2015; Shin et al., 2016). Targeting the role of PIN1 in osteogenesis through pharmacological inhibition has been applied in the study of craniosynostosis due to FGFR2 mutation (S252W) in mice modeling Apert syndrome, suggesting that PIN1 is important for FGFR2 mutant (S252W)-induced RUNX2 activation (Shin et al., 2018). This is one of the most rewarding outcomes of the intensive research into PIN1 since the original discovery of its function in mitosis (Lu et al., 1996). With much accumulated and everexpanding knowledge, we need up-to-date summaries organized into tables and charts to describe the ever-increasing roles of PIN1 and its binding partners, so that more studies are inspired. The idea that PIN1 could be used as a molecular switch and the concept of PIN1 catalyzing by lowering the energy barrier for cis- and trans- isomerization for pS/pT-P, accelerating the conversion up to a 1,000-fold, has been previously proposed (Liou et al., 2011). In this Research Topic, Chen et al. summarizes the understanding of how PIN1 is regulated, with a comprehensive table on the post-translational modifications (PTMs) of PIN1, including phosphorylation, oxidation, SUMOylation, and ubiquitination. How PTMs regulate PIN1 enzymatic activity, binding ability, localization, and function, and how the deregulation of PIN1 PTMs contribute to the development of cancer and Alzheimer’s disease (AD), are reiterated and conceptualized. Therapeutic options and the challenge for targeting PIN1 PTMs with possible drug candidates are also discussed.