Please use this identifier to cite or link to this item: https://doi.org/10.1038/onc.2011.463
Title: Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis
Authors: Chen, H.-Z.
Li, L.
Wang, W.-J.
Du, X.-D.
Wen, Q.
He, J.-P.
Zhao, B.-X.
Li, G.-D.
Zhou, W.
Xia, Y.
Yang, Q.-Y. 
Hew, C.-L. 
Liou, Y.-C. 
Wu, Q.
Keywords: cell proliferation
orphan receptor TR3
phosphorylation
prolyl isomerase pin1
Issue Date: 7-Jun-2012
Citation: Chen, H.-Z., Li, L., Wang, W.-J., Du, X.-D., Wen, Q., He, J.-P., Zhao, B.-X., Li, G.-D., Zhou, W., Xia, Y., Yang, Q.-Y., Hew, C.-L., Liou, Y.-C., Wu, Q. (2012-06-07). Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene 31 (23) : 2876-2887. ScholarBank@NUS Repository. https://doi.org/10.1038/onc.2011.463
Abstract: Pin1 regulates a subset of phosphoproteins by isomerizing phospho-Ser/Thr-Pro motifs via a post-phosphorylation mechanism. Here, we characterize TR3 as a novel Pin1 substrate, and the mitogenic function of TR3 depends on Pin1-induced isomerization. There are at least three phospho-Ser-Pro motifs on TR3 that bind to Pin1. The Ser95-Pro motif of TR3 is the key site through which Pin1 enhances TR3 stability by retarding its degradation. Pin1 can also catalyze TR3 through phospho-Ser431-Pro motif, which is phosphorylated by extracellular signal-regulated kinase 2 (ERK2), resulting in enhanced TR3 transactivation. Furthermore, Pin1 not only facilitates TR3 targeting to the promoter of cyclin D2, a novel downstream target of TR3, but also promotes TR3 to recruit p300, thereby inducing cell proliferation. Importantly, we found that Pin1 is indispensable for TR3 to promote tumor growth both in vitro and in vivo. Our study thus suggests that Pin1 has an important role in cell proliferation by isomerizing TR3. © 2012 Macmillan Publishers Limited All rights reserved.
Source Title: Oncogene
URI: http://scholarbank.nus.edu.sg/handle/10635/101468
ISSN: 09509232
DOI: 10.1038/onc.2011.463
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