title: Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis.
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.
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian, PR China.
authors: H-Z
authors: HZ
authors: Chen
authors: L
authors: L
authors: Li
authors: W-J
authors: WJ
authors: Wang
authors: X-D
authors: XD
authors: Du
authors: Q
authors: Q
authors: Wen
authors: J-P
authors: JP
authors: He
authors: B-X
authors: BX
authors: Zhao
authors: G-D
authors: GD
authors: Li
authors: W
authors: W
authors: Zhou
authors: Y
authors: Y
authors: Xia
authors: Q-Y
authors: QY
authors: Yang
authors: C-L
authors: CL
authors: Hew
authors: Y-C
authors: YC
authors: Liou
authors: Q
authors: Q
authors: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D056742:Cyclin D2 / Q000378:metabolism; D004151:Dipeptides / Q000737:chemistry*; D050687:E2F1 Transcription Factor / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013237:Stereoisomerism; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D056742:Cyclin D2; D004151:Dipeptides; D050687:E2F1 Transcription Factor; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D034741:RNA, Small Interfering; C465983:seryl-proline; D008156:Luciferases; D050880:p300-CBP Transcription Factors; D019950:Mitogen-Activated Protein Kinase 1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse