Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis

被引：44

作者：

Chen, H-Z ^{[1
]}

Li, L. ^{[1
]}

Wang, W-J ^{[1
]}

Du, X-D ^{[1
]}

Wen, Q. ^{[1
]}

He, J-P ^{[1
]}

Zhao, B-X ^{[1
]}

Li, G-D ^{[1
]}

Zhou, W. ^{[2
]}

Xia, Y. ^{[2
]}

Yang, Q-Y ^{[2
]}

Hew, C-L ^{[2
]}

Liou, Y-C ^{[2
]}

Wu, Q. ^{[1
]}

机构：

[1] Xiamen Univ, State Key Lab Cellular Stress Biol, Sch Life Sci, Xiamen 361005, Fujian, Peoples R China

[2] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore

来源：

ONCOGENE | 2012年 / 31卷 / 23期

基金：

中国国家自然科学基金;

关键词：

prolyl isomerase pin1; orphan receptor TR3; phosphorylation; cell proliferation; N-TERMINAL KINASE; CANCER CELL; NEGATIVE REGULATION; GROWTH-FACTORS; NGFI-B; APOPTOSIS; PHOSPHORYLATION; SUBSTRATE; TRANSLOCATION; DOMAINS;

D O I：

10.1038/onc.2011.463

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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. Oncogene (2012) 31, 2876-2887; doi:10.1038/onc.2011.463; published online 17 October 2011

引用

页码：2876 / 2887

页数：12

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