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


: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.






Chen HZ,Li L,Wang WJ,Du XD,Wen Q,He JP,Zhao BX,Li GD,Zhou W,Xia Y,Yang QY,Hew CL,Liou YC,Wu Q




Has Abstract


2012-06-07 00:00:00
















  • Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression.

    abstract::The transcription factor Cdx1 regulates intestine-specific gene expression and enterocyte differentiation. It has been hypothesized to play a role in regulating intestinal cell proliferation; however, the mechanism for this effect remains elusive. In a prior study, we demonstrated that Cdx1 expression reduced the prol...


    pub_type: 杂志文章


    authors: Lynch J,Keller M,Guo RJ,Yang D,Traber P

    更新日期:2003-09-25 00:00:00

  • Na+,HCO3--cotransporter NBCn1 (Slc4a7) accelerates ErbB2-induced breast cancer development and tumor growth in mice.

    abstract::Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na+,HCO3--cotransporter NBCn1 (Slc4a7) to intracellular a...


    pub_type: 杂志文章


    authors: Lee S,Axelsen TV,Jessen N,Pedersen SF,Vahl P,Boedtkjer E

    更新日期:2018-10-01 00:00:00

  • siRNA screening identifies differences in the Fanconi anemia pathway in BALB/c-Trp53+/- with susceptibility versus C57BL/6-Trp53+/- mice with resistance to mammary tumors.

    abstract::BALB/c mice heterozygous for Trp53 develop a high proportion of spontaneous mammary tumors, a phenotype distinct from other mouse strains. BALB/c-Trp53+/- female mice, thus, resemble the hereditary Li-Fraumeni syndrome (LFS) characterized by early-onset of breast cancer, even though LFS involves TP53 mutations, which ...


    pub_type: 杂志文章


    authors: Böhringer M,Obermeier K,Griner N,Waldraff D,Dickinson E,Eirich K,Schindler D,Hagen M,Jerry DJ,Wiesmüller L

    更新日期:2013-11-28 00:00:00

  • Cytokine control of developmental programs in normal hematopoiesis and leukemia.

    abstract::The establishment of a system for in vitro clonal development of hematopoietic cells made it possible to discover the cytokines that regulate hematopoiesis. These cytokines include colony stimulating factors and others, which interact in a network, and there is a cytokine cascade which couples growth and differentiati...


    pub_type: 杂志文章,评审


    authors: Lotem J,Sachs L

    更新日期:2002-05-13 00:00:00

  • BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases.

    abstract::BRCA1, a familial breast and ovarian cancer susceptibility gene encodes nuclear phosphoproteins that function as tumor suppressors in human breast cancer cells. Previously, we have shown that overexpression of a BRCA1 splice variant BRCA1a accelerates apoptosis in human breast cancer cells. In an attempt to determine ...


    pub_type: 杂志文章


    authors: Wang H,Shao N,Ding QM,Cui J,Reddy ES,Rao VN

    更新日期:1997-07-10 00:00:00

  • Loss of the tumor suppressor, Tp53, enhances the androgen receptor-mediated oncogenic transformation and tumor development in the mouse prostate.

    abstract::Recent genome analysis of human prostate cancers demonstrated that both AR gene amplification and TP53 mutation are among the most frequently observed alterations in advanced prostate cancer. However, the biological role of these dual genetic alterations in prostate tumorigenesis is largely unknown. In addition, there...


    pub_type: 杂志文章


    authors: He Y,Johnson DT,Yang JS,Wu H,You S,Yoon J,Lee DH,Kim WK,Aldahl J,Le V,Hooker E,Yu EJ,Geradts J,Cardiff RD,Sun Z

    更新日期:2019-09-01 00:00:00

  • Altered expression of Erg and Ets-2 transcription factors is associated with genetic changes at 21q22.2-22.3 in immortal and cervical carcinoma cell lines.

    abstract::Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved. Altered expression of the ets family transcription factors erg an...


    pub_type: 杂志文章


    authors: Simpson S,Woodworth CD,DiPaolo JA

    更新日期:1997-05-08 00:00:00

  • Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016.

    abstract::The expression of the NH2 terminally truncated ErbB2 receptor (p95ErbB2) in breast cancer correlates with metastatic disease progression compared with the expression of full-length p185ErbB2. We now show that heregulin (HRG), but not EGF, stimulates p95ErbB2 phosphorylation in BT474 breast cancer cells. Furthermore, p...


    pub_type: 杂志文章


    authors: Xia W,Liu LH,Ho P,Spector NL

    更新日期:2004-01-22 00:00:00

  • ARHI is a Ras-related small G-protein with a novel N-terminal extension that inhibits growth of ovarian and breast cancers.

    abstract::Our group recently identified Ras homolog member I (ARHI), a novel maternally imprinted tumor suppressor gene that encodes a 26 kDa GTP-binding protein with high homology to Ras and Rap. Unlike other Ras family members, ARHI exhibits several unusual structural and functional properties. ARHI contains a unique 34 amino...


    pub_type: 杂志文章


    authors: Luo RZ,Fang X,Marquez R,Liu SY,Mills GB,Liao WS,Yu Y,Bast RC

    更新日期:2003-05-15 00:00:00

  • Transcriptional activation of the hepatocyte growth factor receptor (c-met) gene by its ligand (hepatocyte growth factor) is mediated through AP-1.

    abstract::Hepatocyte Growth Factor (HGF) exerts its biological effects via binding and activating a transmembrane protein tyrosine kinase receptor known as c-Met. Previous studies from our laboratory demonstrated that c-met gene expression is inducible by its own ligand (HGF). However, the molecular mechanism(s) involved in thi...


    pub_type: 杂志文章


    authors: Seol DW,Chen Q,Zarnegar R

    更新日期:2000-02-24 00:00:00

  • Transformation by v-Myb.

    abstract::The v-myb oncogene of the avian myeloblastosis virus (AMV) is unique among known oncogenes in that it causes only acute leukemia in animals and transforms only hematopoietic cells in culture. AMV was discovered in the 1930s as a virus that caused a disease in chickens that is similar to acute myelogenous leukemia in h...


    pub_type: 杂志文章,评审


    authors: Lipsick JS,Wang DM

    更新日期:1999-05-13 00:00:00

  • The role of STATs in myeloid differentiation and leukemia.

    abstract::Myeloid differentiation is a highly regulated process governed by various cytokines, such as EPO, TPO, G-CSF, IL-3, IL-5 and GM-CSF. These cytokines act in part through activation of the STAT transcription factor family. In particular, various isoforms of STAT3 and STAT5 are activated during myeloid differentiation in...


    pub_type: 杂志文章,评审


    authors: Coffer PJ,Koenderman L,de Groot RP

    更新日期:2000-05-15 00:00:00

  • New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin.

    abstract::Telomeres are stabilized, and telomeric DNA is replenished, by the action of the ribonucleoprotein reverse transcriptase telomerase. Telomere capping functions include the ability of telomeres to protect chromosome ends from cellular DNA-damage responses such as cell cycle arrest or apoptosis. This property of telomer...


    pub_type: 杂志文章,评审


    authors: Chan SW,Blackburn EH

    更新日期:2002-01-21 00:00:00

  • Upregulation of histamine receptor H1 promotes tumor progression and contributes to poor prognosis in hepatocellular carcinoma.

    abstract::H1 histamine receptor (H1HR) belongs to the family of rhodopsin-like G-protein-coupled receptors. Recent studies have shown that H1HR expression is increased in several types of cancer. However, its functional roles in tumor progression remain largely unknown, especially in hepatocellular carcinoma (HCC). We found tha...


    pub_type: 杂志文章


    authors: Zhao J,Hou Y,Yin C,Hu J,Gao T,Huang X,Zhang X,Xing J,An J,Wan S,Li J

    更新日期:2020-02-01 00:00:00

  • Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition.

    abstract::Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer and pancreas cancer. IL-17 pro...


    pub_type: 杂志文章


    authors: Zhang Q,Liu S,Parajuli KR,Zhang W,Zhang K,Mo Z,Liu J,Chen Z,Yang S,Wang AR,Myers L,You Z

    更新日期:2017-02-02 00:00:00

  • c-Jun causes focus formation and anchorage-independent growth in culture but is non-tumorigenic.

    abstract::The RCAS retroviral vector was used to express chicken and mouse cellular Jun proteins in chicken embryo fibroblasts. Both mouse and chicken proteins induced foci of transformed cells with low to moderate efficiency compared with viral Jun, but were as effective as the viral protein in promoting anchorage-independent ...


    pub_type: 杂志文章


    authors: Wong WY,Håvarstein LS,Morgan IM,Vogt PK

    更新日期:1992-10-01 00:00:00

  • Src family kinases mediate cytoplasmic retention of activated STAT5 in BCR-ABL-positive cells.

    abstract::Persistent activation of the Abl tyrosine kinase in the BCR-ABL fusion protein is the major cause of chronic myeloid leukemia (CML). Among many other substrates BCR-ABL phosphorylates STAT5 and Src family kinases (SFK). Activated pSTAT5 is essential for initial transformation and maintenance of the disease. Cytokine-i...


    pub_type: 杂志文章


    authors: Chatain N,Ziegler P,Fahrenkamp D,Jost E,Moriggl R,Schmitz-Van de Leur H,Müller-Newen G

    更新日期:2013-08-01 00:00:00

  • Activation of oncogenes in human oral cancer cells: a novel codon 13 mutation of c-H-ras-1 and concurrent amplifications of c-erbB-1 and c-myc.

    abstract::By NIH3T3 transfection assay in conjunction with in vitro transient neomycin selection, activated c-H-ras-1 oncogenes were detected in two squamous cell carcinoma cell lines, ZA and HOC-313, newly established from human oral cancer patients. ZA had a point mutational activation at the 13th codon, this activation of c-...


    pub_type: 杂志文章


    authors: Tadokoro K,Ueda M,Ohshima T,Fujita K,Rikimaru K,Takahashi N,Enomoto S,Tsuchida N

    更新日期:1989-04-01 00:00:00

  • Characterization of factor-independent variants derived from TF-1 hematopoietic progenitor cells: the role of the Raf/MAP kinase pathway in the anti-apoptotic effect of GM-CSF.

    abstract::Human hematopoietic progenitor cells (TF-1) undergo apoptosis upon deprivation of their dependent cytokine. In this report, we have isolated and characterized some spontaneously derived cytokine-independent variants from TF-1 cells. Analysis of several signaling molecules known to be activated by the GM-CSF pathway re...


    pub_type: 杂志文章


    authors: Chao JR,Chen CS,Wang TF,Tseng LH,Tsai JJ,Kuo ML,Yen JJ,Yang Yen HF

    更新日期:1997-02-13 00:00:00

  • Ras-independent activation of Rel-family transcription factors by UVB and TPA in cultured keratinocytes.

    abstract::UV irradiation of mammalian cells results in the activation of transcription factors which mediate induction of early response genes designed to repair and minimise the damage sustained by the cell. Evidence from studies in HeLa cells suggest that UVC regulates NF-kappa B activity via tyrosine kinases and activation o...


    pub_type: 杂志文章


    authors: Tobin D,Nilsson M,Toftgård R

    更新日期:1996-02-15 00:00:00

  • Human T-cell leukemia virus type 1 Tax attenuates gamma-irradiation-induced apoptosis through physical interaction with Chk2.

    abstract::Checkpoint kinase 2 (Chk2) is known to mediate diverse cellular responses to genotoxic stress. The fundamental role of Chk2 is to regulate the network of genome-surveillance pathways that coordinate cell-cycle progression with DNA repair and cell survival or death. Defects in Chk2 contribute to the development of both...


    pub_type: 杂志文章


    authors: Park HU,Jeong SJ,Jeong JH,Chung JH,Brady JN

    更新日期:2006-01-19 00:00:00

  • Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma.

    abstract::We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions an...


    pub_type: 杂志文章


    authors: El-Naggar AK,Coombes MM,Batsakis JG,Hong WK,Goepfert H,Kagan J

    更新日期:1998-06-11 00:00:00

  • Epigenetic silencing of the dual-role signal mediator, ANGPTL4 in tumor tissues and its overexpression in the urothelial carcinoma microenvironment.

    abstract::Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell ...


    pub_type: 杂志文章


    authors: Hsieh HY,Jou YC,Tung CL,Tsai YS,Wang YH,Chi CL,Lin RI,Hung SK,Chuang YM,Wu SF,Li C,Shen CH,Chan MWY,Hsu CD

    更新日期:2018-02-01 00:00:00

  • Screening for mutations in exon 11 of the BRCA1 gene in 70 Italian breast and ovarian cancer patients by protein truncation test.

    abstract::The most common mutations in the familial breast and ovarian cancer susceptibility gene BRCA1 are frameshift and nonsense mutations, which lead to the synthesis of truncated proteins. On this ground, we have analysed BRCA1 exon 11, which includes about 61% of coding region, in germline DNA from 70 Italian breast and/o...


    pub_type: 杂志文章


    authors: De Benedetti VM,Radice P,Mondini P,Spatti G,Conti A,Illeni MT,Caligo MA,Cipollini G,Bevilaqua G,Pilotti S,Pierotti MA

    更新日期:1996-09-19 00:00:00

  • Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer.

    abstract::Axl is a receptor that induces proliferation, migration and invasion in cancer. In this study, we show that specific microRNAs (miRNAs) target the 3'-UTR of Axl. Luciferase-reporter assays with wild-type and deleted miR-34 and miR-199a/b seed sequences of Axl 3'-UTR confirmed the specificity of targeting. An inverse c...


    pub_type: 杂志文章


    authors: Mudduluru G,Ceppi P,Kumarswamy R,Scagliotti GV,Papotti M,Allgayer H

    更新日期:2011-06-23 00:00:00

  • ErbB3 upregulation by the HNSCC 3D microenvironment modulates cell survival and growth.

    abstract::Head and neck squamous carcinomas (HNSCC) present as dense epithelioid three-dimensional (3D) tumor nests that can mediate signals via the human epidermal growth factor receptor (ErbB) tyrosine kinase family to promote intratumoral survival and growth. We examined the role of the tumor microenvironment on ErbB recepto...


    pub_type: 杂志文章


    authors: Humtsoe JO,Pham E,Louie RJ,Chan DA,Kramer RH

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  • Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin.

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    pub_type: 杂志文章


    authors: Robanus-Maandag E,Giovannini M,van der Valk M,Niwa-Kawakita M,Abramowski V,Antonescu C,Thomas G,Berns A

    更新日期:2004-08-26 00:00:00

  • CHK1 overexpression in T-cell acute lymphoblastic leukemia is essential for proliferation and survival by preventing excessive replication stress.

    abstract::Checkpoint kinase 1 (CHK1) is a key component of the ATR (ataxia telangiectasia-mutated and Rad3-related)-dependent DNA damage response pathway that protect cells from replication stress, a cell intrinsic phenomenon enhanced by oncogenic transformation. Here, we show that CHK1 is overexpressed and hyperactivated in T-...


    pub_type: 杂志文章


    authors: Sarmento LM,Póvoa V,Nascimento R,Real G,Antunes I,Martins LR,Moita C,Alves PM,Abecasis M,Moita LF,Parkhouse RM,Meijerink JP,Barata JT

    更新日期:2015-06-04 00:00:00

  • Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer.

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    pub_type: 杂志文章


    authors: Caldwell ME,DeNicola GM,Martins CP,Jacobetz MA,Maitra A,Hruban RH,Tuveson DA

    更新日期:2012-03-22 00:00:00

  • Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: the role of the chromatin structure and AP-1 composition.

    abstract::The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely linked with a non-tumorigenic phenotype in somatic cell hybrids made between the human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa and normal human fibroblasts. In contrast, MCP-1 transcription is absent in tumor...


    pub_type: 杂志文章


    authors: Finzer P,Soto U,Delius H,Patzelt A,Coy JF,Poustka A,zur Hausen H,Rösl F

    更新日期:2000-07-06 00:00:00