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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.
Yang, Q. 
Low, C.B.
Karthik, B.C.
Wang, Y. 
Ryo, A.
Yao, S.Q. 
Yang, D. 
Liou, Y.-C. 
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.
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
ISSN: 00219258
DOI: 10.1074/jbc.M109.022814
Appears in Collections:Staff Publications

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