TRF1 controls telomere length and mitotic fidelity in epithelial homeostasis.

Abstract:

:TRF1 is a component of the shelterin complex at mammalian telomeres; however, a role for TRF1 in telomere biology in the context of the organism is unclear. In this study, we generated mice with transgenic TRF1 expression targeted to epithelial tissues (K5TRF1 mice). K5TRF1 mice have shorter telomeres in the epidermis than wild-type controls do, and these are rescued in the absence of the XPF nuclease, indicating that TRF1 acts as a negative regulator of telomere length by controlling XPF activity at telomeres, similar to what was previously described for TRF2-overexpressing mice (K5TRF2 mice). K5TRF1 cells also show increased end-to-end chromosomal fusions, multitelomeric signals, and increased telomere recombination, indicating an impact of TRF1 on telomere integrity, again similar to the case in K5TRF2 cells. Intriguingly, K5TRF1 cells, but not K5TRF2 cells, show increased mitotic spindle aberrations. TRF1 colocalizes with the spindle assembly checkpoint proteins BubR1 and Mad2 at mouse telomeres, indicating a link between telomeres and the mitotic spindle. Together, these results demonstrate that TRF1, like TRF2, negatively regulates telomere length in vivo by controlling the action of the XPF nuclease at telomeres; in addition, TRF1 has a unique role in the mitotic spindle checkpoint.

journal_name

Mol Cell Biol

authors

Muñoz P,Blanco R,de Carcer G,Schoeftner S,Benetti R,Flores JM,Malumbres M,Blasco MA

doi

10.1128/MCB.01339-08

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

1608-25

issue

6

eissn

0270-7306

issn

1098-5549

pii

MCB.01339-08

journal_volume

29

pub_type

杂志文章
  • Proteasomal inhibition attenuates transcriptional activity of hypoxia-inducible factor 1 (HIF-1) via specific effect on the HIF-1alpha C-terminal activation domain.

    abstract::The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth fa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00552-06

    authors: Kaluz S,Kaluzová M,Stanbridge EJ

    更新日期:2006-08-01 00:00:00

  • Endothelial-cell-specific regulation of von Willebrand factor gene expression.

    abstract::In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.2.999

    authors: Jahroudi N,Lynch DC

    更新日期:1994-02-01 00:00:00

  • The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation.

    abstract::The receptors for thyroid hormone (T3R), all-trans-retinoic acid (RAR), and 9-cis-retinoic acid (RXR) bind DNA response elements as homo- and heterodimers. The ligand-binding domains of these receptors contain nine conserved heptads proposed to play a role in dimerization. Mutant receptors with changes in the first or...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.9.5725

    authors: Au-Fliegner M,Helmer E,Casanova J,Raaka BM,Samuels HH

    更新日期:1993-09-01 00:00:00

  • Postcleavage sequence specificity in V(D)J recombination.

    abstract::Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.14.5032-5040.2000

    authors: Agard EA,Lewis SM

    更新日期:2000-07-01 00:00:00

  • AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae.

    abstract::The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis. The function of AFR1 was investigated by engineering cells to constitutively express AFR1 without...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.2.723

    authors: Konopka JB,DeMattei C,Davis C

    更新日期:1995-02-01 00:00:00

  • Human gene (c-fes) related to the onc sequences of Snyder-Theilen feline sarcoma virus.

    abstract::The onc gene (v-fes) of the acutely transforming feline sarcoma virus (Snyder-Theilen strain) has homologous cellular sequences (c-fes) in all vertebrate species, including humans. We isolated from a human DNA library recombinant phages containing overlapping c-fes sequences. The human c-fes locus spans a region of 3....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.8.1014

    authors: Franchini G,Gelmann EP,Dalla-Favera R,Gallo RC,Wong-Staal F

    更新日期:1982-08-01 00:00:00

  • Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling.

    abstract::The Ras-RAF-mitogen-activated protein kinase (Ras-RAF-MAPK) pathway is overactive in many cancers and in some developmental disorders. In one of those disorders, namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins. We show that these mut...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01636-09

    authors: Molzan M,Schumacher B,Ottmann C,Baljuls A,Polzien L,Weyand M,Thiel P,Rose R,Rose M,Kuhenne P,Kaiser M,Rapp UR,Kuhlmann J,Ottmann C

    更新日期:2010-10-01 00:00:00

  • Inhibition of nonsense-mediated RNA decay activates autophagy.

    abstract::Nonsense-mediated RNA decay (NMD) is an mRNA surveillance mechanism which rapidly degrades select cytoplasmic mRNAs. We and others have shown that NMD is a dynamically regulated process inhibited by amino acid deprivation, hypoxia, and other cellular stresses commonly generated by the tumor microenvironment. This inhi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00174-13

    authors: Wengrod J,Martin L,Wang D,Frischmeyer-Guerrerio P,Dietz HC,Gardner LB

    更新日期:2013-06-01 00:00:00

  • Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin.

    abstract::Wnt glycoproteins play essential roles in the development of metazoan organisms. Many Wnt proteins, such as Wnt1, activate the well-conserved canonical Wnt signaling pathway, which results in accumulation of beta-catenin in the cytosol and nucleus. Other Wnts, such as Wnt5a, activate signaling mechanisms which do not ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.11.4757-4768.2004

    authors: González-Sancho JM,Brennan KR,Castelo-Soccio LA,Brown AM

    更新日期:2004-06-01 00:00:00

  • Ligand-induced repression of the glucocorticoid receptor gene is mediated by an NCoR1 repression complex formed by long-range chromatin interactions with intragenic glucocorticoid response elements.

    abstract::Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01151-12

    authors: Ramamoorthy S,Cidlowski JA

    更新日期:2013-05-01 00:00:00

  • Functional role of laminin carbohydrate.

    abstract::Previous work showed that tunicamycin suppresses glycosylation of laminin. In the present work, the role of glycosylation in the secretion of laminin and in the disulfide bonding of laminin subunits was studied, using tunicamycin to inhibit glycosylation. Tunicamycin inhibited extensively the secretion of laminin into...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.1.1

    authors: Howe CC

    更新日期:1984-01-01 00:00:00

  • Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer.

    abstract::A prominent hallmark of most human cancer is aneuploidy, which is a result of the chromosomal instability of cancer cells and is thought to contribute to the initiation and progression of most carcinomas. The developmentally regulated GATA6 transcription factor is commonly lost in ovarian cancer, and the loss of its e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00087-09

    authors: Capo-chichi CD,Cai KQ,Testa JR,Godwin AK,Xu XX

    更新日期:2009-09-01 00:00:00

  • A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain.

    abstract::Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the B...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.5.1733-1746.2000

    authors: Kobayashi A,Yamagiwa H,Hoshino H,Muto A,Sato K,Morita M,Hayashi N,Yamamoto M,Igarashi K

    更新日期:2000-03-01 00:00:00

  • The cellular response to neuregulins is governed by complex interactions of the erbB receptor family.

    abstract::Deregulated signaling by the four members of the epidermal growth factor receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze signaling by these receptors have been hampered by the diversity of ligands and extensive interreceptor cross ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.10.5770

    authors: Riese DJ 2nd,van Raaij TM,Plowman GD,Andrews GC,Stern DF

    更新日期:1995-10-01 00:00:00

  • Identification of phosphotyrosine-containing proteins in untransformed and Rous sarcoma virus-transformed chicken embryo fibroblasts.

    abstract::Phosphorylation on tyrosine residues mediated by pp60src appears to be a primary biochemical event leading to the establishment of the transformed phenotype in Rous sarcoma virus (RSV)-infected cells. To identify the cellular proteins that undergo tyrosine phosphorylation during transformation, a 32P-labeled RSV-trans...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.6.653

    authors: Martinez R,Nakamura KD,Weber MJ

    更新日期:1982-06-01 00:00:00

  • The Saccharomyces cerevisiae mutation elm4-1 facilitates pseudohyphal differentiation and interacts with a deficiency in phosphoribosylpyrophosphate synthase activity to cause constitutive pseudohyphal growth.

    abstract::Saccharomyces cerevisiae mutant E124 was selected in a visual screen based on elongated cell shape. Genetic analysis showed that E124 contains two separate mutations, pps1-1 and elm4-1, each causing a distinct phenotype inherited as a single-gene trait. In rich medium, pps1-1 by itself causes increased doubling time b...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.7.4671

    authors: Blacketer MJ,Madaule P,Myers AM

    更新日期:1994-07-01 00:00:00

  • Genetic analysis reveals different functions for the products of the thyroid hormone receptor alpha locus.

    abstract::Thyroid hormone receptors are encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) loci. These genes are transcribed into multiple variants whose functions are unclear. Analysis by gene inactivation in mice has provided new insights into the functional complexity of these products. Different strategies designed to modify...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.14.4748-4760.2001

    authors: Gauthier K,Plateroti M,Harvey CB,Williams GR,Weiss RE,Refetoff S,Willott JF,Sundin V,Roux JP,Malaval L,Hara M,Samarut J,Chassande O

    更新日期:2001-07-01 00:00:00

  • At the revolution with Fred Sherman.

    abstract::Fred Sherman was a prominent yeast geneticist and my mentor in graduate school. Fred passed away in September 2013 at the age of 81. In this minireview, I describe what it was like to know Fred and be in his lab from 1977 to 1982, the extraordinarily exciting time when the recombinant DNA revolution hit yeast genetics...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.01682-13

    authors: Zaret KS

    更新日期:2014-03-01 00:00:00

  • Overexpression of c-Myc alters G(1)/S arrest following ionizing radiation.

    abstract::Study of the mechanism(s) of genomic instability induced by the c-myc proto-oncogene has the potential to shed new light on its well-known oncogenic activity. However, an underlying mechanism(s) for this phenotype is largely unknown. In the present study, we investigated the effects of c-Myc overexpression on the DNA ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.6.1819-1833.2002

    authors: Sheen JH,Dickson RB

    更新日期:2002-03-01 00:00:00

  • Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase.

    abstract::"Neutropenia" refers to deficient numbers of neutrophils, the most abundant type of white blood cell. Two main forms of inherited neutropenia are cyclic neutropenia, in which neutrophil counts oscillate with a 21-day frequency, and severe congenital neutropenia, in which static neutropenia may evolve at times into leu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00596-09

    authors: Salipante SJ,Rojas ME,Korkmaz B,Duan Z,Wechsler J,Benson KF,Person RE,Grimes HL,Horwitz MS

    更新日期:2009-08-01 00:00:00

  • Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling.

    abstract::The Src homology 2-containing phosphotyrosine phosphatase (SHP2) is primarily a positive effector of receptor tyrosine kinase signaling. However, the molecular mechanism by which SHP2 effects its biological function is unknown. In this report, we provide evidence that defines the molecular mechanism and site of action...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.21.7875-7886.2003

    authors: Agazie YM,Hayman MJ

    更新日期:2003-11-01 00:00:00

  • Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak.

    abstract::Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore ge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.14.5235-5247.2002

    authors: Chandrasekharan S,Qiu TH,Alkharouf N,Brantley K,Mitchell JB,Liu ET

    更新日期:2002-07-01 00:00:00

  • A Feedback Loop between MicroRNA 155 (miR-155), Programmed Cell Death 4, and Activation Protein 1 Modulates the Expression of miR-155 and Tumorigenesis in Tongue Cancer.

    abstract::MicroRNA 155 (miR-155) is an oncomir, generated as a noncoding RNA from the BIC gene whose promoter activity is mainly controlled via activation protein 1 (AP-1) and NF-κB transcription factors. We found that the expression levels of miR-155 and programmed cell death 4 (Pdcd4) exhibit inverse relationships in tongue c...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00410-18

    authors: Zargar S,Tomar V,Shyamsundar V,Vijayalakshmi R,Somasundaram K,Karunagaran D

    更新日期:2019-03-01 00:00:00

  • Tissue localization of Drosophila melanogaster ras transcripts during development.

    abstract::Three ras homologs have been identified in Drosophila melanogaster. Here we describe the tissue distribution of their transcripts as analyzed by in situ hybridization. The RNAs of the three genes show a similar distribution at every developmental stage examined. In embryos, the transcripts are uniformly distributed. I...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.6.2241

    authors: Segal D,Shilo BZ

    更新日期:1986-06-01 00:00:00

  • Interaction of p53 with its consensus DNA-binding site.

    abstract::We have analyzed the specific interaction of murine p53 with the consensus DNA-binding sequence 5'-AGACATGCCT-AGACATGCCT-3'. We used segments of p53 lacking the C-terminal, nonspecific DNA-binding domain because the presence of an autonomous nonspecific DNA-binding domain in wild-type p53 would complicate analysis of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.4.2157

    authors: Wang Y,Schwedes JF,Parks D,Mann K,Tegtmeyer P

    更新日期:1995-04-01 00:00:00

  • Properties and possible functions of the adenylate cyclase in plasma membranes of Saccharomyces cerevisiae.

    abstract::We have examined the possible role of adenosine 3',5'-phosphate (cAMP) in functions associated with the plasma membranes of Saccharomyces cerevisiae. Purified membranes from this source contained an adenylate cyclase which was insensitive to activation by fluoride or guanine nucleotides, only weakly responsive to chan...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.12.1481

    authors: Jaynes PK,McDonough JP,Mahler HR

    更新日期:1982-12-01 00:00:00

  • TATA-box DNA binding activity and subunit composition for RNA polymerase III transcription factor IIIB from Xenopus laevis.

    abstract::The RNA polymerase III transcription initiation factor TFIIIB contains the TATA-box-binding protein (TBP) and polymerase III-specific TBP-associated factors (TAFs). Previous studies have shown that DNA oligonucleotides containing the consensus TATA-box sequence inhibit polymerase III transcription, implying that the D...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.9.4639

    authors: McBryant SJ,Meier E,Leresche A,Sharp SJ,Wolf VJ,Gottesfeld JM

    更新日期:1996-09-01 00:00:00

  • Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

    abstract::Keratins K5 and K14 form the extensive intermediate filament network of mitotically active basal cells in all stratified epithelia. We have explored the regulatory mechanisms governing cell-type-specific and differentiation stage-specific expression of the human K5 gene in transiently transfected keratinocytes in vitr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.6.3176

    authors: Byrne C,Fuchs E

    更新日期:1993-06-01 00:00:00

  • Construction of an opal suppressor by oligonucleotide-directed mutagenesis of a Saccharomyces cerevisiae tRNA(Trp) gene.

    abstract::In vitro mutagenesis was used to create putative opal suppressor alleles of a tRNA(Trp) gene of Saccharomyces cerevisiae. The construct with the requisite anticodon change did not result in an active suppressor, whereas when a second change was introduced into the portion of the gene encoding the intron, an active and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.8.4379

    authors: Atkin AL,Roy KL,Bell JB

    更新日期:1990-08-01 00:00:00

  • Structure of the gene for CAD, the multifunctional protein that initiates UMP synthesis in Syrian hamster cells.

    abstract::Two adjacent fragments of genomic DNA spanning the gene for CAD, which encodes the first three enzymes of UMP biosynthesis, were cloned from a mutant Syrian hamster cell line containing multiple copies of this gene. The mutant was selected for resistance to N-(phosphonacetyl)-L-aspartate, a potent and specific inhibit...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.3.293

    authors: Padgett RA,Wahl GM,Stark GR

    更新日期:1982-03-01 00:00:00