Separation of telomerase functions by reverse genetics.

Abstract:

:The canonical function of the human telomerase protein (hTERT) is to synthesize telomeric DNA, but it has other biological activities, including enhancing cell proliferation, decreasing apoptosis, regulating DNA damage responses, and increasing cellular proliferative lifespan. The mechanistic relationships among these activities are not understood. We previously demonstrated that ectopic hTERT expression in primary human mammary epithelial cells diminishes their requirement for exogenous mitogens, thus giving them a proliferative advantage in a mitogen-depleted environment. Here, we show that this phenotype is caused by a combination of increased cell division and decreased apoptosis. In addition, we use a panel of hTERT mutants to demonstrate that this enhanced cell proliferation can be uncoupled not only from telomere elongation, but also from other telomerase activities, including cellular lifespan extension and regulation of DNA damage responses. We also find that the proliferative function of hTERT, which requires hTERT catalytic activity, is not caused by increased Wnt signaling, but is accompanied by alterations in key cell cycle regulators and is linked to an hTERT-catalyzed decrease in the levels of the RNA component of mitochondrial RNA processing endoribonuclease. Thus, enhanced cell proliferation is an independent function of hTERT that could provide a new target for the development of anti-telomerase cancer therapeutic agents.

authors

Mukherjee S,Firpo EJ,Wang Y,Roberts JM

doi

10.1073/pnas.1112414108

subject

Has Abstract

pub_date

2011-12-13 00:00:00

pages

E1363-71

issue

50

eissn

0027-8424

issn

1091-6490

pii

1112414108

journal_volume

108

pub_type

杂志文章
  • Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15.

    abstract::Previous work has shown that serotonin induces an increase in membrane K+ conductance in Aplysia neuron R15 and that this response is mediated by cAMP. The present study examines the role of protein phosphorylation in the response to serotonin. A specific inhibitor of cAMP-dependent protein kinase was injected intrace...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.12.3877

    authors: Adams WB,Levitan IB

    更新日期:1982-06-01 00:00:00

  • Thymosin corrects the abnormal DNA synthetic response of NZB mouse thymocytes.

    abstract::New Zealand Black (NZB) mice develop after 16 weeks of age an autoimmune and lymphoproliferative disease which is a model for systemic lupus erythematosus and lymphoid malignancy in humans. At this age, the mice manifest a progressive decline in T lymphocyte (thymus-derived lymphocyte) functions and serum thymosin lev...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.7.2637

    authors: Dauphinee MJ,Talal N,Goldstein AL,White A

    更新日期:1974-07-01 00:00:00

  • Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity.

    abstract::Efficient and productive virus infection often requires viral countermeasures that block innate immunity. The IFN-inducible 2',5'-oligoadenylate (2-5A) synthetases (OASs) and ribonuclease (RNase) L are components of a potent host antiviral pathway. We previously showed that murine coronavirus (MHV) accessory protein n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1306917110

    authors: Zhang R,Jha BK,Ogden KM,Dong B,Zhao L,Elliott R,Patton JT,Silverman RH,Weiss SR

    更新日期:2013-08-06 00:00:00

  • Introduction to quantum turbulence.

    abstract::The term quantum turbulence denotes the turbulent motion of quantum fluids, systems such as superfluid helium and atomic Bose-Einstein condensates, which are characterized by quantized vorticity, superfluidity, and, at finite temperatures, two-fluid behavior. This article introduces their basic properties, describes t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type:

    doi:10.1073/pnas.1400033111

    authors: Barenghi CF,Skrbek L,Sreenivasan KR

    更新日期:2014-03-25 00:00:00

  • Host specificity of DNA produced by Escherichia coli. XI. In vitro modification of phage fd replicative form.

    abstract::An enzymatic activity, having the properties expected of a B-specific host-controlled modification enzyme, has been purified from an extract of Escherichia coli strain B. This activity renders the unmodified replicative form of phage fd resistant to B-specific restriction and is only present in strains carrying intact...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.63.2.556

    authors: Kühnlein U,Linn S,Arber W

    更新日期:1969-06-01 00:00:00

  • Radiocarbon and DNA evidence for a pre-Columbian introduction of Polynesian chickens to Chile.

    abstract::Two issues long debated among Pacific and American prehistorians are (i) whether there was a pre-Columbian introduction of chicken (Gallus gallus) to the Americas and (ii) whether Polynesian contact with South America might be identified archaeologically, through the recovery of remains of unquestionable Polynesian or...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.0703993104

    authors: Storey AA,Ramírez JM,Quiroz D,Burley DV,Addison DJ,Walter R,Anderson AJ,Hunt TL,Athens JS,Huynen L,Matisoo-Smith EA

    更新日期:2007-06-19 00:00:00

  • The chemodiversity of wines can reveal a metabologeography expression of cooperage oak wood.

    abstract::Wine chemical compositions, which result from a complex interplay between environmental factors, genetic factors, and viticultural practices, have mostly been studied using targeted analyses of selected families of metabolites. Detailed studies have particularly concerned volatile and polyphenolic compounds because of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0901100106

    authors: Gougeon RD,Lucio M,Frommberger M,Peyron D,Chassagne D,Alexandre H,Feuillat F,Voilley A,Cayot P,Gebefügi I,Hertkorn N,Schmitt-Kopplin P

    更新日期:2009-06-09 00:00:00

  • A Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold.

    abstract::Chlamydia trachomatis R2c is the prototype for a recently discovered group of ribonucleotide reductase R2 proteins that use a heterodinuclear Mn/Fe redox cofactor for radical generation and storage. Here, we show that the Mycobacterium tuberculosis protein Rv0233, an R2 homologue and a potential virulence factor, cont...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0812971106

    authors: Andersson CS,Högbom M

    更新日期:2009-04-07 00:00:00

  • Identification, purification, and molecular cloning of autonomously replicating sequence-binding protein 1 from fission yeast Schizosaccharomyces pombe.

    abstract::Autonomously replicating sequence (ARS) elements of the fission yeast Schizosaccharomyces pombe contain multiple imperfect copies of the consensus sequence reported by Maundrell et al. [Maundrell K., Hutchison, A. & Shall, S. (1988) EMBO J. 7, 2203-2209]. When cell free extracts of S. pombe were incubated with a dimer...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.1.502

    authors: Murakami Y,Huberman JA,Hurwitz J

    更新日期:1996-01-09 00:00:00

  • The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas.

    abstract::Splice variants (SVs) of receptors for growth hormone-releasing hormone (GHRH) have been found in primary human prostate cancers and diverse human cancer cell lines. GHRH antagonists inhibit growth of various experimental human cancers, including pancreatic and colorectal, xenografted into nude mice or cultured in vit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.182433099

    authors: Busto R,Schally AV,Varga JL,Garcia-Fernandez MO,Groot K,Armatis P,Szepeshazi K

    更新日期:2002-09-03 00:00:00

  • Peroxisome proliferator-activated receptor delta promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage.

    abstract::Significant attention has focused on the role of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, recent advances have identified triglyceride-rich lipoproteins [e.g., very LDL (VLDL)] as independent risk predictors for this disease. We have previously demonstrated peroxisome proliferator...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0510815103

    authors: Lee CH,Kang K,Mehl IR,Nofsinger R,Alaynick WA,Chong LW,Rosenfeld JM,Evans RM

    更新日期:2006-02-14 00:00:00

  • Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis.

    abstract::Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1108220109

    authors: Sebastián D,Hernández-Alvarez MI,Segalés J,Sorianello E,Muñoz JP,Sala D,Waget A,Liesa M,Paz JC,Gopalacharyulu P,Orešič M,Pich S,Burcelin R,Palacín M,Zorzano A

    更新日期:2012-04-03 00:00:00

  • Hearing regulates Drosophila aggression.

    abstract::Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melano...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1605946114

    authors: Versteven M,Vanden Broeck L,Geurten B,Zwarts L,Decraecker L,Beelen M,Göpfert MC,Heinrich R,Callaerts P

    更新日期:2017-02-21 00:00:00

  • Motion of a slightly compressible fluid.

    abstract::We show that the motion of a slightly compressible fluid is near that of an incompressible fluid. That is, for a given initial velocity field, the motion of a compressible fluid with large sound speed is near to that of an idealized incompressible fluid. We consider the compressible fluid motion in Lagrangian coordina...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.2.539

    authors: Ebin DG

    更新日期:1975-02-01 00:00:00

  • The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy.

    abstract::Heat shock protein 90-alpha (Hsp90alpha) is an intracellular molecular chaperone. However, it can also be secreted with the underlying regulatory mechanism remaining far from clear. Here we show that the secreted Hsp90alpha is a C-terminal truncated form and its secretion is regulated by the C-terminal EEVD motif via ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0908151106

    authors: Wang X,Song X,Zhuo W,Fu Y,Shi H,Liang Y,Tong M,Chang G,Luo Y

    更新日期:2009-12-15 00:00:00

  • Visualization of opiate receptor upregulation by light microscopy autoradiography.

    abstract::Light microscopy autoradiography has been used to visualize neuroanatomical patterns of brain opiate receptor upregulation in response to chronic naltrexone administration. Slide-mounted brain sections of frozen rat brain were labeled in vitro with dihydro[3H]morphine, a relatively selective mu opioid ligand. The grea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.12.3893

    authors: Tempel A,Gardner EL,Zukin RS

    更新日期:1984-06-01 00:00:00

  • Structurally intact (78-kDa) forms of maternal lactoferrin purified from urine of preterm infants fed human milk: identification of a trypsin-like proteolytic cleavage event in vivo that does not result in fragment dissociation.

    abstract::Two forms of lactoferrin, an intact lactoferrin and a "nicked" but apparently intact (i.e., 78-kDa) form, have been isolated from the urine of preterm infants fed human milk. These two forms of lactoferrin, demonstrated to be entirely of maternal origin, were copurified using affinity columns of immobilized single-str...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.8.2994

    authors: Hutchens TW,Henry JF,Yip TT

    更新日期:1991-04-15 00:00:00

  • Binding of the phytotoxin zinniol stimulates the entry of calcium into plant protoplasts.

    abstract::Zinniol [1,2-bis(hydroxymethyl)-3-methoxy-4-methyl-5-(3-methyl-2-butenyloxy)benzene], a toxin produced by fungi of the Alternaria group, causes symptoms in plants that resemble those induced by the fungi. The phytotoxin binds to carrot protoplasts and isolated membranes in a saturable and reversible manner. Receptor o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.16.5932

    authors: Thuleau P,Graziana A,Rossignol M,Kauss H,Auriol P,Ranjeva R

    更新日期:1988-08-01 00:00:00

  • Components of fitness become effectively neutral in equilibrium populations.

    abstract::If, because of trade-offs or similar considerations, components of fitness are negatively correlated in equilibrium populations, they may then exhibit no correlation with total fitness. Lack of correlation with fitness is a fundamental characteristic of selective neutrality. Hence, selectively important traits become ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.5.2018

    authors: Reeve R,Smith E,Wallace B

    更新日期:1990-03-01 00:00:00

  • Neurotrophic factor for central neurons.

    abstract::A serum-free culture of dissociated neurons from embryonic rat hippocampus has been established as a rapid and quantitative in vitro test system for neurotrophic signals in the mammalian brain. By means of this cell culture bioassay, a novel low molecular weight neurotrophic factor (NTF) could be identified. NTF is es...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.4.1248

    authors: Müller HW,Beckh S,Seifert W

    更新日期:1984-02-01 00:00:00

  • Conversion of lowland tropical forests to tree cash crop plantations loses up to one-half of stored soil organic carbon.

    abstract::Tropical deforestation for the establishment of tree cash crop plantations causes significant alterations to soil organic carbon (SOC) dynamics. Despite this recognition, the current Intergovernmental Panel on Climate Change (IPCC) tier 1 method has a SOC change factor of 1 (no SOC loss) for conversion of forests to p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1504628112

    authors: van Straaten O,Corre MD,Wolf K,Tchienkoua M,Cuellar E,Matthews RB,Veldkamp E

    更新日期:2015-08-11 00:00:00

  • Mechanism for discrimination between viral and host mRNA in interferon-treated cells.

    abstract::In extracts of interferon-treated HeLa cells, RNA covalently linked to double-stranded RNA (dsRNA) is preferentially degraded compared with mRNA not linked in dsRNA. This was established by following the degradation of poly(A)-containing mRNA annealed with poly(U), of poly(C)-containing encephalomyocarditis virus RNA ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.6.2600

    authors: Nilsen TW,Baglioni C

    更新日期:1979-06-01 00:00:00

  • Age-dependent deficiency in import of mitochondrial DNA glycosylases required for repair of oxidatively damaged bases.

    abstract::The mitochondria are the major source of chronic oxidative stress, which has been implicated in the aging process. Along with other cellular changes, aged cells accumulate mutations in both their nuclear and mitochondrial genomes, and they contain increased amounts of oxidatively damaged mutagenic bases such as 7,8-di...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1932854100

    authors: Szczesny B,Hazra TK,Papaconstantinou J,Mitra S,Boldogh I

    更新日期:2003-09-16 00:00:00

  • Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors.

    abstract::The rat anterior pituitary gland (AP) receives all of its blood supply via the hypophyseal portal circulation. We now report, in rats with estradiol (E2)-induced prolactin-secreting tumors, that newly formed arteries directly supply the AP and that this arteriogenesis is closely correlated with the sensitivity of two ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.14.4549

    authors: Elias KA,Weiner RI

    更新日期:1984-07-01 00:00:00

  • Signaling by N- and C-terminal sequences of parathyroid hormone-related protein in hippocampal neurons.

    abstract::Parathyroid hormone-related protein (PTHrP) is synthesized in the brain, and a single type of cloned receptor for the N-terminal portion of PTHrP and PTH is present in the central nervous system. Nothing is known about the physiological actions or signaling pathways used by PTHrP in the brain. Using cultured rat hippo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.22.10182

    authors: Fukayama S,Tashjian AH Jr,Davis JN,Chisholm JC

    更新日期:1995-10-24 00:00:00

  • A brain sexual dimorphism controlled by adult circulating androgens.

    abstract::Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a pos...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.13.7538

    authors: Cooke BM,Tabibnia G,Breedlove SM

    更新日期:1999-06-22 00:00:00

  • Quorum decision-making facilitates information transfer in fish shoals.

    abstract::Despite the growing interest in collective phenomena such as "swarm intelligence" and "wisdom of the crowds," little is known about the mechanisms underlying decision-making in vertebrate animal groups. How do animals use the behavior of others to make more accurate decisions, especially when it is not possible to ide...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710344105

    authors: Ward AJ,Sumpter DJ,Couzin ID,Hart PJ,Krause J

    更新日期:2008-05-13 00:00:00

  • Individual differences versus social dynamics in the formation of animal dominance hierarchies.

    abstract::Linear hierarchies, the classical pecking-order structures, are formed readily in both nature and the laboratory in a great range of species including humans. However, the probability of getting linear structures by chance alone is quite low. In this paper we investigate the two hypotheses that are proposed most often...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.082104199

    authors: Chase ID,Tovey C,Spangler-Martin D,Manfredonia M

    更新日期:2002-04-16 00:00:00

  • Gating charge interactions with the S1 segment during activation of a Na+ channel voltage sensor.

    abstract::Voltage-gated Na(+) channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltage-driven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1116449108

    authors: DeCaen PG,Yarov-Yarovoy V,Scheuer T,Catterall WA

    更新日期:2011-11-15 00:00:00

  • Cyclic polyamides for recognition in the minor groove of DNA.

    abstract::Small molecules that specifically bind with high affinity to any designated DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to rationally alter the sequence specificity of minor groove-binding polyamides containing N-methyl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.22.10389

    authors: Cho J,Parks ME,Dervan PB

    更新日期:1995-10-24 00:00:00