title: Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins.
abstract: Pin1 is a highly conserved enzyme that only isomerizes specific phosphorylated Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes. Such conformational changes represent a novel and tightly controlled signaling mechanism regulating a spectrum of protein activities in physiology and disease; often through phosphorylation-dependent, ubiquitin-mediated proteasomal degradation. In this review, we summarize recent advances in elucidating the role and regulation of Pin1 in controlling protein stability. We also propose a mechanism by which Pin1 functions as a molecular switch to control the fates of phosphoproteins. We finally stress the need to develop tools to visualize directly Pin1-catalyzed protein conformational changes as a way to determine their roles in the development and treatment of human diseases.
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543. dbslyc@nus.edu.sg
authors.forename: Yih-Cherng
authors.initials: YC
authors.lastname: Liou
authors.forename: Xiao Zhen
authors.initials: XZ
authors.lastname: Zhou
authors.forename: Kun Ping
authors.initials: KP
authors.lastname: Lu
mesh_terms: D000375:Aging; D015870:Gene Expression; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009369:Neoplasms / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D055550:Protein Stability; D059748:Proteolysis; D016615:Telomere / Q000378:metabolism
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010750:Phosphoproteins; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase