Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.


:Although cyclin D1 is overexpressed in a significant number of human cancers, overexpression alone is insufficient to promote tumorigenesis. In vitro studies have revealed that inhibition of cyclin D1 nuclear export unmasks its neoplastic potential. Cyclin D1 nuclear export depends upon phosphorylation of a C-terminal residue, threonine 286, (Thr-286) which in turn promotes association with the nuclear exportin, CRM1. Mutation of Thr-286 to a non-phosphorylatable residue results in a constitutively nuclear cyclin D1 protein with significantly increased oncogenic potential. To determine whether cyclin D1 is subject to mutations that inhibit its nuclear export in human cancer, we have sequenced exon 5 of cyclin D1 in primary esophageal carcinoma samples and in cell lines derived from esophageal cancer. Our work reveals that cyclin D1 is subject to mutations in primary human cancer. The mutations identified specifically disrupt phosphorylation of cyclin D1 at Thr-286, thereby enforcing nuclear accumulation of cyclin D1. Through characterization of these mutants, we also define an acidic residue within the C-terminus of cyclin D1 that is necessary for recognition and phosphorylation of cyclin D1 by glycogen synthase kinase-3 beta. Finally, through construction of compound mutants, we demonstrate that cell transformation by the cancer-derived cyclin D1 alleles correlates with their ability to associate with and activate CDK4. Our data reveal that cyclin D1 is subject to mutations in primary human cancer that specifically disrupt phosphorylation-dependent nuclear export of cyclin D1 and suggest that such mutations contribute to the genesis and progression of neoplastic growth.






Benzeno S,Lu F,Guo M,Barbash O,Zhang F,Herman JG,Klein PS,Rustgi A,Diehl JA




Has Abstract


2006-10-12 00:00:00
















  • Simple sequence repeat polymorphism within the p53 gene.

    abstract::This report describes a new polymorphism, in intron 3 of the p53 gene, which consists of a single repeat of 16 nucleotides, absent in the published wild-type p53 gene sequence. In the Caucasian population tested (n = 82), 28% of individuals were heterozygotes for this polymorphism. Using PCR-based analysis, we were ab...


    pub_type: 杂志文章


    authors: Lazar V,Hazard F,Bertin F,Janin N,Bellet D,Bressac B

    更新日期:1993-06-01 00:00:00

  • Characterization of the cell membrane-associated products of the Neuregulin 4 gene.

    abstract::The NRG4 gene is a member of a family of four genes that encode a class of epidermal growth factors. This gene has been reported to express a protein designated here as NRG4A1. We describe here a novel splice variant of the NRG4 gene, NRG4A2, which encodes a C-terminal region containing a predicted type I PDZ-binding ...


    pub_type: 杂志文章


    authors: Hayes NV,Newsam RJ,Baines AJ,Gullick WJ

    更新日期:2008-01-24 00:00:00

  • DNA binding and selective gene induction by different forms of the p53 protein.

    abstract::P53 is a tumor suppressor gene that plays a crucial role in suppressing tumorigenesis by inducing either cell cycle arrest or apoptosis in cells with DNA damage. In more than 50% of tumors p53 is inactivated by gene mutations. However, there have also been reports of tumor cells in which p53 remains wild type and is p...


    pub_type: 杂志文章


    authors: Mayelzadeh F,Martinez JD

    更新日期:2007-05-10 00:00:00

  • Identification of heterologous translocation partner genes fused to the BCL6 gene in diffuse large B-cell lymphomas: 5'-RACE and LA - PCR analyses of biopsy samples.

    abstract::In order to elucidate the molecular mechanism(s) for BCL6 translocation, we identified translocational partner genes by subjecting clinical biopsy samples from patients with non-Hodgkin's lymphoma to 5'-rapid amplification of cDNA ends (5'-RACE). Sequence analysis of the 5'-RACE product revealed that the BCL6 gene was...


    pub_type: 杂志文章


    authors: Yoshida S,Kaneita Y,Aoki Y,Seto M,Mori S,Moriyama M

    更新日期:1999-12-23 00:00:00

  • The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells.

    abstract::Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell...


    pub_type: 杂志文章


    authors: Tada Y,Yamaguchi Y,Kinjo T,Song X,Akagi T,Takamura H,Ohta T,Yokota T,Koide H

    更新日期:2015-02-05 00:00:00

  • MicroRNA dysregulation in gastric cancer: a new player enters the game.

    abstract::Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Recent discoveries have shed new light on the involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer. A substantial number of miRNAs show ...


    pub_type: 杂志文章,评审


    authors: Wu WK,Lee CW,Cho CH,Fan D,Wu K,Yu J,Sung JJ

    更新日期:2010-10-28 00:00:00

  • Induction of telomerase activity by UV-irradiation in Chinese hamster cells.

    abstract::Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during canc...


    pub_type: 杂志文章


    authors: Hande MP,Balajee AS,Natarajan AT

    更新日期:1997-10-02 00:00:00

  • Constitutive activation of the shh-ptc1 pathway by a patched1 mutation identified in BCC.

    abstract::Mutations in the transmembrane receptor patched1 (ptc1) are responsible for the majority of basal cell carcinoma (BCC) cases. Many of these mutations, including ptc1-Q688X, result in premature truncation of the ptc1 protein. ptc1-Q688X has been identified in patients with both BCC and nevoid basal cell carcinoma syndr...


    pub_type: 杂志文章


    authors: Barnes EA,Heidtman KJ,Donoghue DJ

    更新日期:2005-01-27 00:00:00

  • The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.

    abstract::The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss als...


    pub_type: 杂志文章


    authors: Hunter JE,Butterworth JA,Zhao B,Sellier H,Campbell KJ,Thomas HD,Bacon CM,Cockell SJ,Gewurz BE,Perkins ND

    更新日期:2016-06-30 00:00:00

  • Latent infection with Kaposi's sarcoma-associated herpesvirus enhances retrotransposition of long interspersed element-1.

    abstract::Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), a gamma-2 herpesvirus, is the causative agent of KS, primary effusion lymphoma (PEL), and a plasma cell variant of multicentric Castleman's disease. Although KSHV latency is detected in KS-related tumors, oncogenic pathways activated by KSHV latent infection are not...


    pub_type: 杂志文章


    authors: Nakayama R,Ueno Y,Ueda K,Honda T

    更新日期:2019-05-01 00:00:00

  • Cdc25A phosphatase suppresses apoptosis induced by serum deprivation.

    abstract::The phosphatase Cdc25A was shown to be a target of the transcription factor c-Myc. Myc-induced apoptosis appeared dependent on Cdc25A expression and Cdc25A over-expression could substitute for Myc-triggered apoptosis. These findings suggested that an important downstream component of Myc-mediated apoptosis was identif...


    pub_type: 杂志文章


    authors: Fuhrmann G,Leisser C,Rosenberger G,Grusch M,Huettenbrenner S,Halama T,Mosberger I,Sasgary S,Cerni C,Krupitza G

    更新日期:2001-07-27 00:00:00

  • Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas.

    abstract::We report chromosome 3p deletion mapping of 32 cervical carcinoma (CC) biopsies using 26 microsatellite markers located in frequently deleted 3p regions to detect loss of heterozygosity and homozygous loss. In addition, two STS markers (NLJ-003 and NL3-001) located in the 3p21.3 telomeric (3p21.3T) and 3p21.3 centrome...


    pub_type: 杂志文章


    authors: Senchenko V,Liu J,Braga E,Mazurenko N,Loginov W,Seryogin Y,Bazov I,Protopopov A,Kisseljov FL,Kashuba V,Lerman MI,Klein G,Zabarovsky ER

    更新日期:2003-05-15 00:00:00

  • Vital functions for lethal caspases.

    abstract::Caspases are a family of cysteine proteases expressed as inactive zymogens in virtually all animal cells. These enzymes play a central role in most cell death pathways leading to apoptosis but growing evidences implicate caspases also in nonapoptotic functions. Several of these enzymes, activated in molecular platform...


    pub_type: 杂志文章,评审


    authors: Launay S,Hermine O,Fontenay M,Kroemer G,Solary E,Garrido C

    更新日期:2005-08-04 00:00:00

  • Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration.

    abstract::While studying Bim, a BH3-only proapoptotic protein, we identified an approximately 36 kDa protein, which was abundantly expressed in all five strains of primary normal human prostate (NHP) epithelial cells but significantly reduced or lost in seven prostate cancer cell lines. The approximately 36 kDa protein was subs...


    pub_type: 杂志文章


    authors: Liu JW,Shen JJ,Tanzillo-Swarts A,Bhatia B,Maldonado CM,Person MD,Lau SS,Tang DG

    更新日期:2003-03-13 00:00:00

  • Reduced ability of transforming growth factor-alpha to induce EGF receptor heterodimerization and downregulation suggests a mechanism of oncogenic synergy with ErbB2.

    abstract::The epidermal growth factor receptor (EGFR) is activated by a variety of ligands including EGF and transforming growth factor-alpha (TGFalpha), whereas no ligand for the homologous ErbB2 oncoprotein has yet been identified. Here we use both an ErbB2 phosphoantibody (aPY1222) and an activation-specific EGFR antibody to...


    pub_type: 杂志文章


    authors: Gulliford TJ,Huang GC,Ouyang X,Epstein RJ

    更新日期:1997-10-01 00:00:00

  • Modulation of p53 dependent gene expression and cell death through thioredoxin-thioredoxin reductase by the Interferon-Retinoid combination.

    abstract::We have shown earlier that the IFN-beta and all-trans retinoic acid (RA) combination, but not the single agents, induces death in several tumor cell lines. Employing a genetic technique we have identified several Genes associated with Retinoid-IFN induced Mortality (GRIM). One of the GRIMs was human thioredoxin reduct...


    pub_type: 杂志文章


    authors: Hu J,Ma X,Lindner DJ,Karra S,Hofmann ER,Reddy SP,Kalvakolanu DV

    更新日期:2001-07-12 00:00:00

  • Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface.

    abstract::The C-type lectin domain containing group 14 family members CLEC14A and CD93 are proteins expressed by endothelium and are implicated in tumour angiogenesis. CD248 (alternatively known as endosialin or tumour endothelial marker-1) is also a member of this family and is expressed by tumour-associated fibroblasts and pe...


    pub_type: 杂志文章


    authors: Khan KA,Naylor AJ,Khan A,Noy PJ,Mambretti M,Lodhia P,Athwal J,Korzystka A,Buckley CD,Willcox BE,Mohammed F,Bicknell R

    更新日期:2017-11-02 00:00:00

  • High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice.

    abstract::Individuals affected with the Gorlin syndrome inherit a germ-line mutation of the patched (Ptc1) developmental gene and, analogously to Ptc1 heterozygous mice, show an increased susceptibility to spontaneous tumor development. Human and mouse Ptc1 heterozygotes (Ptc1(+/-)) are also hypersensitive to ionizing radiation...


    pub_type: 杂志文章


    authors: Pazzaglia S,Mancuso M,Atkinson MJ,Tanori M,Rebessi S,Majo VD,Covelli V,Hahn H,Saran A

    更新日期:2002-10-24 00:00:00

  • Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth.

    abstract::Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide (CRAMP), are important effectors of the innate immune system with direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this stu...


    pub_type: 杂志文章


    authors: Li D,Beisswenger C,Herr C,Schmid RM,Gallo RL,Han G,Zakharkina T,Bals R

    更新日期:2014-05-22 00:00:00

  • Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1.

    abstract::Loss-of-function mutations in the LKB1 (STK11) serine-threonine kinase gene cause Peutz-Jeghers syndrome, which is associated with inherited susceptibility to colorectal and other cancers. No downstream targets of LKB1 kinase activity have been identified. Here we show that LKB1 can direct the phosphorylation of the s...


    pub_type: 杂志文章


    authors: Spicer J,Rayter S,Young N,Elliott R,Ashworth A,Smith D

    更新日期:2003-07-24 00:00:00

  • HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction of NF-kB with other transcription factor families.

    abstract::The trans-activator protein, tax, from the human T leukemia virus type 1 (HTLV-1) trans-activates both viral and cellular genes. It has previously been shown that granulocyte macrophage-colony stimulating factor (GM-CSF) is constitutively expressed in HTLV-1 infected cells and in cells artificially expressing tax. We ...


    pub_type: 杂志文章


    authors: Himes SR,Coles LS,Katsikeros R,Lang RK,Shannon MF

    更新日期:1993-12-01 00:00:00

  • FBXL14 abolishes breast cancer progression by targeting CDCP1 for proteasomal degradation.

    abstract::Understanding the molecular mechanisms that underlie the aggressive behavior and relapse of breast cancer may help in the development of novel therapeutic interventions. CUB-domain-containing protein 1 (CDCP1), a transmembrane adaptor protein, is highly maintained and required in the context of cellular metastatic pot...


    pub_type: 杂志文章


    authors: Cui YH,Kim H,Lee M,Yi JM,Kim RK,Uddin N,Yoo KC,Kang JH,Choi MY,Cha HJ,Kwon OS,Bae IH,Kim MJ,Kaushik N,Lee SJ

    更新日期:2018-10-01 00:00:00

  • Hepatitis C virus-induced activation of β-catenin promotes c-Myc expression and a cascade of pro-carcinogenetic events.

    abstract::Chronic infection by hepatitis C virus (HCV) is a major risk factor for the onset and development of hepatocellular carcinoma (HCC), although the underlying mechanisms are unclear. The c-Myc oncogene contributes to the genesis of many types of cancers, including HCC, partly via the induction of genetic damage and the ...


    pub_type: 杂志文章


    authors: Higgs MR,Lerat H,Pawlotsky JM

    更新日期:2013-09-26 00:00:00

  • Induction of epithelial abnormalities that resemble human breast lesions by the expression of the neu/erbB-2 oncogene in reconstituted mouse mammary gland.

    abstract::We have developed a transplantation system that allows us to introduce oncogenes into mouse mammary epithelial cells in culture and then to reconstitute an epithelial tree in vivo from the genetically altered cells. Introduction of the neu oncogene, a transforming homologue of the human proto-oncogene c-erbB-2, produc...


    pub_type: 杂志文章


    authors: Bradbury JM,Arno J,Edwards PA

    更新日期:1993-06-01 00:00:00

  • Repression of hepatitis B virus (HBV) transgene and HBV-induced liver injury by low protein diet.

    abstract::Persistent infection with hepatitis B virus (HBV) is one of the primary risk factors for human hepatocellular carcinoma (HCC). In a human ecological study, we have shown that, in addition to HBV, animal food consumption also significantly contributes to the variance of HCC. To test the interacting effect of HBV and an...


    pub_type: 杂志文章


    authors: Hu JF,Cheng Z,Chisari FV,Vu TH,Hoffman AR,Campbell TC

    更新日期:1997-12-04 00:00:00

  • Stable expression of intracellular Notch suppresses v-Src-induced transformation in avian neural cells.

    abstract::Understanding how disruption of differentiation contributes to the cancer cell phenotype is required to identify alterations essential for malignant transformation and provide experimental basis for their correction. We investigated whether primary quail neuroretina cells, transformed by a conditional v-Src mutant (QN...


    pub_type: 杂志文章


    authors: Mateos S,Amarir S,Laugier D,Marx M,Calothy G

    更新日期:2007-05-17 00:00:00

  • Determinants of sequence-specific DNA-binding by p48v-myb.

    abstract::The v-myb oncogene of the avian myeloblastosis virus encodes a nuclear protein, p48v-myb, which binds to DNA in a sequence-specific manner. We have used wild type and mutant forms of this protein expressed in E. coli to study the protein and DNA determinants for sequence-specific DNA-binding. We have shown that only t...


    pub_type: 杂志文章


    authors: Garcia A,LaMontagne K,Reavis D,Stober-Grässer U,Lipsick JS

    更新日期:1991-02-01 00:00:00

  • How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations.

    abstract::Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with furth...


    pub_type: 杂志文章


    authors: Rehrauer H,Wu L,Blum W,Pecze L,Henzi T,Serre-Beinier V,Aquino C,Vrugt B,de Perrot M,Schwaller B,Felley-Bosco E

    更新日期:2018-05-01 00:00:00

  • The PGC-1/ERR signaling axis in cancer.

    abstract::Proliferating cells need to produce a large amount of energy and, at the same time, need to maintain a constant supply of biosynthetic precursors of macromolecules that are used as building blocks for generating new cells. Indeed, many cancer cells undergo a switch from mitochondrial to glycolytic metabolism and displ...


    pub_type: 杂志文章,评审


    authors: Deblois G,St-Pierre J,Giguère V

    更新日期:2013-07-25 00:00:00

  • A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23).

    abstract::A distinctive subset of renal carcinomas is associated with Xp11. 2 translocations and resulting TFE3 gene fusions (PRCC-TFE3, PSF-TFE3, NONO-TFE3, ASPL-TFE3), encoding related aberrant transcription factors. We report the cloning of a novel clathrin heavy-chain gene (CLTC)-TFE3 gene fusion resulting from a t(X;17)(p1...


    pub_type: 杂志文章


    authors: Argani P,Lui MY,Couturier J,Bouvier R,Fournet JC,Ladanyi M

    更新日期:2003-08-14 00:00:00