Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles.


:Loss of cell cycle control and acquisition of chromosomal rearrangements such as gene amplification often occur during tumor progression, suggesting that they may be correlated. We show here that the wild-type p53 allele is lost when fibroblasts from patients with the Li-Fraumeni syndrome (LFS) are passaged in vitro. Normal and LFS cells containing wild-type p53 arrested in G1 when challenged with the uridine biosynthesis inhibitor PALA and did not undergo PALA-selected gene amplification. The converse occurred in cells lacking wild-type p53 expression. Expression of wild-type p53 in transformants of immortal and tumor cells containing mutant p53 alleles restored G1 control and reduced the frequency of gene amplification to undetectable levels. These studies reveal that p53 contributes to a metabolically regulated G1 check-point, and they provide a model for understanding how abnormal cell cycle progression leads to the genetic rearrangements involved in tumor progression.






Yin Y,Tainsky MA,Bischoff FZ,Strong LC,Wahl GM




Has Abstract


1992-09-18 00:00:00
















  • Cellular ras activity and phospholipid metabolism.

    abstract::Cellular ras activity has been neutralized in 3T3 cells by microinjection of a specific anti-ras monoclonal antibody. The injected antibody efficiently inhibited proliferation in cells treated with a phorbol ester and a calcium ionophore, or with prostaglandin F2 alpha. These treatments were designed to imitate the ac...


    pub_type: 杂志文章


    authors: Yu CL,Tsai MH,Stacey DW

    更新日期:1988-01-15 00:00:00

  • Café Scientifique--déjà vu.

    abstract::Is the Café Scientifique a fashionable by-product of a comfortable age or an indicator of the changing relationship between science and society? ...


    pub_type: 杂志文章


    authors: Dallas D

    更新日期:2006-07-28 00:00:00

  • BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.

    abstract::Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond inde...


    pub_type: 杂志文章


    authors: Welz PS,Zinna VM,Symeonidi A,Koronowski KB,Kinouchi K,Smith JG,Guillén IM,Castellanos A,Furrow S,Aragón F,Crainiciuc G,Prats N,Caballero JM,Hidalgo A,Sassone-Corsi P,Benitah SA

    更新日期:2019-05-30 00:00:00

  • Regulation of the microtubule steady state in vitro by ATP.

    abstract::ATP increases microtubule steady state assembly and disassembly rates in vitro in a concentration-dependent manner. Bovine brain microtubules, composed of 75% tubulin and 25% high molecular weight microtubule-associated proteins (MAPs), were purified by three cycles of assembly and disassembly in the absence of ATP. W...


    pub_type: 杂志文章


    authors: Margolis RL,Wilson L

    更新日期:1979-11-01 00:00:00

  • Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration.

    abstract::Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient r...


    pub_type: 杂志文章


    authors: Cohn RD,Henry MD,Michele DE,Barresi R,Saito F,Moore SA,Flanagan JD,Skwarchuk MW,Robbins ME,Mendell JR,Williamson RA,Campbell KP

    更新日期:2002-09-06 00:00:00

  • TFIIH plays an essential role in RNA polymerase I transcription.

    abstract::TFIIH is a multisubunit protein complex that plays an essential role in nucleotide excision repair and transcription of protein-coding genes. Here, we report that TFIIH is also required for ribosomal RNA synthesis in vivo and in vitro. In yeast, pre-rRNA synthesis is impaired in TFIIH ts strains. In a mouse, part of c...


    pub_type: 杂志文章


    authors: Iben S,Tschochner H,Bier M,Hoogstraten D,Hozák P,Egly JM,Grummt I

    更新日期:2002-05-03 00:00:00

  • Family of proteins that interact with TFIID and regulate promoter activity.

    abstract::A family of proteins was shown to bind cooperatively with TFIID to core promoters, as previously demonstrated for the general initiation factor TFIIA. These factors form distinct complexes with TFIID, fail to bind DNA in the absence of TFIID, differ chromatographically from TFIIA, and compete with TFIIA for binding to...


    pub_type: 杂志文章


    authors: Meisterernst M,Roeder RG

    更新日期:1991-11-01 00:00:00

  • Hsp104 gives clients the individual attention they need.

    abstract::Yeast heat shock protein 104 (Hsp104), the only known eukaryotic disaggregase, remodels both disordered protein aggregates and cross-β sheet amyloids. To handle this diverse clientele, DeSantis et al. report that Hsp104 hexamers use distinct mechanisms-individual subunits are able to dissolve disordered aggregates, bu...


    pub_type: 评论,杂志文章


    authors: Murray AN,Kelly JW

    更新日期:2012-11-09 00:00:00

  • A suppressor of TBP mutations encodes an RNA polymerase III transcription factor with homology to TFIIB.

    abstract::The TDS4 gene of S. cerevisiae was isolated as an allele-specific high copy suppressor of mutations within the basic region of the TATA-binding protein (TBP). The gene is essential for viability and encodes a 596 aa protein. The first 300 aa of the TDS4 protein exhibit significant sequence similarity to the RNA polyme...


    pub_type: 杂志文章


    authors: Buratowski S,Zhou H

    更新日期:1992-10-16 00:00:00

  • Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.

    abstract::Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birt...


    pub_type: 杂志文章


    authors: Cox LM,Yamanishi S,Sohn J,Alekseyenko AV,Leung JM,Cho I,Kim SG,Li H,Gao Z,Mahana D,Zárate Rodriguez JG,Rogers AB,Robine N,Loke P,Blaser MJ

    更新日期:2014-08-14 00:00:00

  • The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration.

    abstract::The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of vascular morphogenesis. EphrinB2 may have an active signaling role, resulting in bi-directional signal transduction downstream of both ephrinB2 and Eph receptors. To separate the ligand and receptor-like functio...


    pub_type: 杂志文章


    authors: Adams RH,Diella F,Hennig S,Helmbacher F,Deutsch U,Klein R

    更新日期:2001-01-12 00:00:00

  • Structural Basis for a Safety-Belt Mechanism That Anchors Condensin to Chromosomes.

    abstract::Condensin protein complexes coordinate the formation of mitotic chromosomes and thereby ensure the successful segregation of replicated genomes. Insights into how condensin complexes bind to chromosomes and alter their topology are essential for understanding the molecular principles behind the large-scale chromatin r...


    pub_type: 杂志文章


    authors: Kschonsak M,Merkel F,Bisht S,Metz J,Rybin V,Hassler M,Haering CH

    更新日期:2017-10-19 00:00:00

  • IKKalpha at the crossroads of inflammation and metastasis.

    abstract::The development of solid tumors is regulated by dynamic interactions between evolving neoplastic cells and their microenvironment. Luo et al. (2007) recently demonstrated that tumor-infiltrating immune cells expressing RANKL induce activation and nuclear localization of IKKalpha in prostatic epithelial tumor cells. Th...


    pub_type: 杂志文章


    authors: Affara NI,Coussens LM

    更新日期:2007-04-06 00:00:00

  • Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway.

    abstract::We have generated mice lacking H2-M complexes, critical facilitators of peptide loading onto major histo-compatibility complex class II molecules. Ab molecules in these mice matured into stable complexes and were efficiently expressed at the cell surface. Most carried a single peptide derived from the class II-associa...


    pub_type: 杂志文章


    authors: Miyazaki T,Wolf P,Tourne S,Waltzinger C,Dierich A,Barois N,Ploegh H,Benoist C,Mathis D

    更新日期:1996-02-23 00:00:00

  • A Deep Learning Approach to Antibiotic Discovery.

    abstract::Due to the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover new antibiotics. To address this challenge, we trained a deep neural network capable of predicting molecules with antibacterial activity. We performed predictions on multiple chemical libraries and discovered a molecule fr...


    pub_type: 杂志文章


    authors: Stokes JM,Yang K,Swanson K,Jin W,Cubillos-Ruiz A,Donghia NM,MacNair CR,French S,Carfrae LA,Bloom-Ackermann Z,Tran VM,Chiappino-Pepe A,Badran AH,Andrews IW,Chory EJ,Church GM,Brown ED,Jaakkola TS,Barzilay R,Collins J

    更新日期:2020-02-20 00:00:00

  • Isolation and characterization of sigma(70)-retaining transcription elongation complexes from Escherichia coli.

    abstract::sigma(70) subunit is thought to be released from the core RNA polymerase (RNAP) upon the transition from initiation to elongation or shortly afterward. Here, we identify a population of RNAP from E. coli that retains sigma(70) throughout elongation. The relative amount of this population appears to depend on cellular ...


    pub_type: 杂志文章


    authors: Bar-Nahum G,Nudler E

    更新日期:2001-08-24 00:00:00

  • The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.

    abstract::The mitochondrial unfolded protein response (UPRmt) can be triggered in a cell-non-autonomous fashion across multiple tissues in response to mitochondrial dysfunction. The ability to communicate information about the presence of mitochondrial stress enables a global response that can ultimately better protect an organ...


    pub_type: 杂志文章


    authors: Zhang Q,Wu X,Chen P,Liu L,Xin N,Tian Y,Dillin A

    更新日期:2018-08-09 00:00:00

  • P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage.

    abstract::The P7C3 class of aminopropyl carbazole chemicals fosters the survival of neurons in a variety of rodent models of neurodegeneration or nerve cell injury. To uncover its mechanism of action, an active derivative of P7C3 was modified to contain both a benzophenone for photocrosslinking and an alkyne for CLICK chemistry...


    pub_type: 杂志文章


    authors: Wang G,Han T,Nijhawan D,Theodoropoulos P,Naidoo J,Yadavalli S,Mirzaei H,Pieper AA,Ready JM,McKnight SL

    更新日期:2014-09-11 00:00:00

  • L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

    abstract::Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-argini...


    pub_type: 杂志文章


    authors: Geiger R,Rieckmann JC,Wolf T,Basso C,Feng Y,Fuhrer T,Kogadeeva M,Picotti P,Meissner F,Mann M,Zamboni N,Sallusto F,Lanzavecchia A

    更新日期:2016-10-20 00:00:00

  • Mutations in the gene for EF-G reduce the requirement for 4.5S RNA in the growth of E. coli.

    abstract::A general strategy is described for the isolation of suppressors of essential genes whose functions are unknown. This strategy was used to analyze the role of 4.5S RNA, an essential RNA of E. coli. In this strategy, the structural gene for 4.5S RNA is fused to the Ptac promoter in such a way that the strain becomes de...


    pub_type: 杂志文章


    authors: Brown S

    更新日期:1987-06-19 00:00:00

  • Hoxa-2 mutant mice exhibit homeotic transformation of skeletal elements derived from cranial neural crest.

    abstract::Mice homozygous for a targeted mutation of the Hoxa-2 (Hox 1.11) gene are born with cleft palates and die within 24 hr of birth. Analysis of stained skeletons revealed that homozygous mutant animals contained multiple cranial skeletal defects, including a duplication of the ossification centers of the bones of the mid...


    pub_type: 杂志文章


    authors: Gendron-Maguire M,Mallo M,Zhang M,Gridley T

    更新日期:1993-12-31 00:00:00

  • Identification of base mismatches recognized by the heteroduplex-DNA-repair system of Streptococcus pneumoniae.

    abstract::The susceptibility to repair of particular base mismatches by the hex system of Streptococcus pneumoniae was examined by comparison of the nucleotide sequence of the wild-type and eight mutant alleles of the malM gene. A detailed restriction map was constructed for pLS70, and the nucleotide sequence was determined for...


    pub_type: 杂志文章


    authors: Lacks SA,Dunn JJ,Greenberg B

    更新日期:1982-12-01 00:00:00

  • CNS myelin and sertoli cell tight junction strands are absent in Osp/claudin-11 null mice.

    abstract::Oligodendrocyte-specific protein (OSP)/claudin-11 is a recently identified transmembrane protein found in CNS myelin and testis with unknown function. Herein we demonstrate that Osp null mice exhibit both neurological and reproductive deficits: CNS nerve conduction is slowed, hindlimb weakness is conspicuous, and male...


    pub_type: 杂志文章


    authors: Gow A,Southwood CM,Li JS,Pariali M,Riordan GP,Brodie SE,Danias J,Bronstein JM,Kachar B,Lazzarini RA

    更新日期:1999-12-10 00:00:00

  • Vesicle-mediated export and assembly of pore-forming oligomers of the enterobacterial ClyA cytotoxin.

    abstract::The ClyA protein is a pore-forming cytotoxin expressed by Escherichia coli and some other enterobacteria. It confers cytotoxic activity toward mammalian cells, but it has remained unknown how ClyA is surface exposed and exported from bacterial cells. Outer-membrane vesicles (OMVs) released from the bacteria were shown...


    pub_type: 杂志文章


    authors: Wai SN,Lindmark B,Söderblom T,Takade A,Westermark M,Oscarsson J,Jass J,Richter-Dahlfors A,Mizunoe Y,Uhlin BE

    更新日期:2003-10-03 00:00:00

  • The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development.

    abstract::The LIM domain protein rbtn2 is associated with T cell acute leukemias. We demonstrate that rbtn2 is a nuclear protein expressed in the erythroid lineage in vivo, and using homologous recombination, we show that it is essential for erythroid development in mice. The homozygous rbtn2 null mutation leads to failure of y...


    pub_type: 杂志文章


    authors: Warren AJ,Colledge WH,Carlton MB,Evans MJ,Smith AJ,Rabbitts TH

    更新日期:1994-07-15 00:00:00

  • RNA polymerase interactions with the upstream region of the E. coli tyrT promoter.

    abstract::The rate of in vivo transcription from the E. coli tRNA and rRNA promoters depends on both cellular growth rate and aminoacid availability. To investigate the molecular mechanisms involved we determined the extent of interaction of RNA polymerase with the promoter of the tyrT stable RNA gene. We show that the enzyme c...


    pub_type: 杂志文章


    authors: Travers AA,Lamond AI,Mace HA,Berman ML

    更新日期:1983-11-01 00:00:00

  • From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II.

    abstract::RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ∼60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subd...


    pub_type: 杂志文章


    authors: Braberg H,Jin H,Moehle EA,Chan YA,Wang S,Shales M,Benschop JJ,Morris JH,Qiu C,Hu F,Tang LK,Fraser JS,Holstege FC,Hieter P,Guthrie C,Kaplan CD,Krogan NJ

    更新日期:2013-08-15 00:00:00

  • The origin of replication of plasmid p15A and comparative studies on the nucleotide sequences around the origin of related plasmids.

    abstract::Replication of Escherichia coli plasmid p15A was examined by use of a cell extract or a mixture of three purified E. coli enzymes: RNA polymerase; RNAase H; and DNA polymerase I. In each system, replication initiates at any of three consecutive nucleotides located at a unique site. Primer transcription starts 508 bp u...


    pub_type: 杂志文章


    authors: Selzer G,Som T,Itoh T,Tomizawa J

    更新日期:1983-01-01 00:00:00

  • Stem cells on patrol.

    abstract::Hematopoietic stem cells (HSCs) exist in the bone marrow and circulate in the blood. In this issue, Massberg et al. (2007) report that HSCs also travel through the lymphatic system. Furthermore, migration of HSCs--which express Toll-like receptors--allows the recognition of pathogenic molecules in peripheral tissues t...


    pub_type: 评论,杂志文章


    authors: Welner RS,Kincade PW

    更新日期:2007-11-30 00:00:00

  • Raphe Circuits on the Menu.

    abstract::The dorsal raphe nucleus (DRN) is an important brain area for body-weight regulation. In this issue of Cell, Nectow et al. uncover cell-type-specific neural circuitry and pharmacology for appetite control within the DRN. ...


    pub_type: 评论,杂志文章


    authors: Yang H,Sternson SM

    更新日期:2017-07-27 00:00:00