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|Title:||Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process||Authors:||Zhou, W.
|Issue Date:||4-Sep-2009||Citation:||Zhou, W., Yang, Q., Low, C.B., Karthik, B.C., Wang, Y., Ryo, A., Yao, S.Q., Yang, D., Liou, Y.-C. (2009-09-04). Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process. Journal of Biological Chemistry 284 (36) : 23980-23988. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M109.022814||Abstract:||The cis-trans peptidylprolyl isomerase Pin1 plays a critical role in regulating a subset of phosphoproteins by catalyzing conformational changes on the phosphorylated Ser/Thr-Pro motifs. The phosphorylation-directed ubiquitination is one of the major mechanisms to regulate the abundance of p27Kip1. In this study, we demonstrate that Pin1 catalyzes the cis-trans conformational changes of p27Kip1 and further mediates its stability through the polyubiquitination mechanism. Our results show that the phosphorylated Thr-187-Pro motif in p27Kip1 is a key Pin1-binding site. In addition, NMR analyses show that this phosphorylated Thr-187-Pro site undergoes conformational change catalyzed by Pin1. Moreover, in Pin1 knock-out mouse embryonic fibroblasts, p27Kip1 has a shorter lifetime and displays a higher degree of polyubiquitination than in Pin1 wild-type mouse embryonic fibroblasts, suggesting that Pin1 plays a critical role in regulating p27Kip1 degradation. Additionally, Pin1 dramatically reduces the interaction between p27Kip1 and Cks1, possibly via isomerizing the cis-trans conformation of p27Kip1. Our study thus reveals a novel regulatory mechanism for p27Kip1 stability and sheds new light on the biological function of Pin1 as a general regulator of protein stability. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.||Source Title:||Journal of Biological Chemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/94535||ISSN:||00219258||DOI:||10.1074/jbc.M109.022814|
|Appears in Collections:||Staff Publications|
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