Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals.


:The sphingomyelin pathway, which is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide, signals apoptosis for tumor necrosis factor alpha, Fas, and ionizing radiation. In the present studies, the anticancer drug daunorubicin also stimulated ceramide elevation and apoptosis in P388 and U937 cells. Cell-permeable analogs of ceramide, but not other lipid second messengers, mimicked daunorubicin in inducing apoptosis. Daunorubicin-stimulated ceramide elevation, however, did not result from sphingomyelin hydrolysis, but rather from de novo synthesis via activation of the enzyme ceramide synthase. An obligatory role for ceramide synthase was defined, since its natural specific inhibitor, fumonisin B1, blocked daunorubicin-induced ceramide elevation and apoptosis. These studies demonstrate that ceramide synthase activity can be regulated in eukaryotes and constitute definitive evidence for a requirement for ceramide elevation in the induction of apoptosis.






Bose R,Verheij M,Haimovitz-Friedman A,Scotto K,Fuks Z,Kolesnick R




Has Abstract


1995-08-11 00:00:00
















  • Pushing and pulling in prokaryotic DNA segregation.

    abstract::In prokaryotes, DNA can be segregated by three different types of cytoskeletal filaments. The best-understood type of partitioning (par) locus encodes an actin homolog called ParM, which forms dynamically unstable filaments that push plasmids apart in a process reminiscent of mitosis. However, the most common type of ...


    pub_type: 杂志文章,评审


    authors: Gerdes K,Howard M,Szardenings F

    更新日期:2010-06-11 00:00:00

  • Biochemical and genetic characterization of a competence pheromone from B. subtilis.

    abstract::We have purified and characterized a modified peptide pheromone that accumulates in culture medium as B. subtilis grows to high density. This pheromone is required for the development of genetic competence. When added to cells at low density, the pheromone induces the premature development of competence. The peptide m...


    pub_type: 杂志文章


    authors: Magnuson R,Solomon J,Grossman AD

    更新日期:1994-04-22 00:00:00

  • SnapShot: Electrochemical Communication in Biofilms.

    abstract::The role of electricity in biological systems was first appreciated through electrical stimulation experiments performed by Luigi Galvani in the 18th century. These pioneering experiments demonstrated that the behavior of living tissues is governed by the flow of electrochemical species-an insight that gave rise to th...


    pub_type: 杂志文章


    authors: Lee DD,Prindle A,Liu J,Süel GM

    更新日期:2017-06-29 00:00:00

  • Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.

    abstract::The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on t...


    pub_type: 杂志文章


    authors: Symons M,Derry JM,Karlak B,Jiang S,Lemahieu V,Mccormick F,Francke U,Abo A

    更新日期:1996-03-08 00:00:00

  • Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif.

    abstract::We have adopted Drosophila tissue culture cells as a host system for studying the structure and function of mammalian transcription factors. These cells provide an Sp1-deficient background and have been used in a complementation assay to identify functional domains of human transcription factor Sp1. The SV40 early pro...


    pub_type: 杂志文章


    authors: Courey AJ,Tjian R

    更新日期:1988-12-02 00:00:00

  • Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins.

    abstract::Members of the myocyte enhancer factor-2 (MEF2) family of MADS domain transcription factors cannot induce myogenesis in transfected fibroblasts, but when coexpressed with the myogenic basic-helix-loop-helix (bHLH) proteins MyoD or myogenin they dramatically increase the extent of myogenic conversion above that seen wi...


    pub_type: 杂志文章


    authors: Molkentin JD,Black BL,Martin JF,Olson EN

    更新日期:1995-12-29 00:00:00

  • An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene.

    abstract::Multidrug resistance in human cells results from increased expression of the mdr1 (P-glycoprotein) gene. Although the same gene is activated in cells selected with different drugs, multidrug-resistant cell lines can be preferentially resistant to their selecting agent. The mdr1 cDNA sequence from vinblastine-selected ...


    pub_type: 杂志文章


    authors: Choi KH,Chen CJ,Kriegler M,Roninson IB

    更新日期:1988-05-20 00:00:00

  • The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo.

    abstract::HNF-3 beta, a transcription factor of the winged-helix family, is expressed in embryonic and adult endoderm and also in midline cells of the node, notochord, and floor plate in mouse embryos. To define the function of HNF-3 beta, a targeted mutation in the HNF-3 beta locus was generated by homologous recombination in ...


    pub_type: 杂志文章


    authors: Weinstein DC,Ruiz i Altaba A,Chen WS,Hoodless P,Prezioso VR,Jessell TM,Darnell JE Jr

    更新日期:1994-08-26 00:00:00

  • A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus.

    abstract::A strong transcription enhancer was identified in the genomic DNA (235 kb) of human cytomegalovirus (HCMV), a ubiquitous and severe pathogen of the herpesvirus group. Cotransfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-HCMV recombinant viruses that had incorporated overlapping se...


    pub_type: 杂志文章


    authors: Boshart M,Weber F,Jahn G,Dorsch-Häsler K,Fleckenstein B,Schaffner W

    更新日期:1985-06-01 00:00:00

  • Atomic structure of scallop myosin subfragment S1 complexed with MgADP: a novel conformation of the myosin head.

    abstract::The crystal structure of a proteolytic subfragment from scallop striated muscle myosin, complexed with MgADP, has been solved at 2.5 A resolution and reveals an unusual conformation of the myosin head. The converter and the lever arm are in very different positions from those in either the pre-power stroke or near-rig...


    pub_type: 杂志文章


    authors: Houdusse A,Kalabokis VN,Himmel D,Szent-Györgyi AG,Cohen C

    更新日期:1999-05-14 00:00:00

  • Conformational changes in a replication origin induced by an initiator protein.

    abstract::The replication initiator protein of the plasmid R6K binds to seven contiguous 22 bp direct repeats that form an indispensable part of the three replication origins alpha, beta, and gamma. Binding of the initiator to the direct repeats induced a marked bending of the region of gamma replication origin. Binding of the ...


    pub_type: 杂志文章


    authors: Mukherjee S,Patel I,Bastia D

    更新日期:1985-11-01 00:00:00

  • Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death.

    abstract::We have generated mice carrying a germline mutation in the tyrosine kinase catalytic domain of the trkB gene. This mutation eliminates expression of gp145trkB, a protein-tyrosine kinase that serves as the signaling receptor for two members of the nerve growth factor family of neurotrophins, brain-derived neurotrophic ...


    pub_type: 杂志文章


    authors: Klein R,Smeyne RJ,Wurst W,Long LK,Auerbach BA,Joyner AL,Barbacid M

    更新日期:1993-10-08 00:00:00

  • Stem cells and cancer: two faces of eve.

    abstract::Recent evidence suggests that a subset of cancer cells within some tumors, the so-called cancer stem cells, may drive the growth and metastasis of these tumors. Understanding the pathways that regulate proliferation, self-renewal, survival, and differentiation of malignant and normal stem cells may shed light on mecha...


    pub_type: 杂志文章


    authors: Clarke MF,Fuller M

    更新日期:2006-03-24 00:00:00

  • The complete sequence of a chromosomal mouse alpha--globin gene reveals elements conserved throughout vertebrate evolution.

    abstract::The mammalian alpha- and beta--globin genes are thought to have evolved from a common ancestral sequence by a duplication event that occurred over 500 million years ago. We have now determined the entire nucleotide sequence of a cloned mouse alpha--globin gene, including regions that flank and interrupt the coding seq...


    pub_type: 杂志文章


    authors: Nishioka Y,Leder P

    更新日期:1979-11-01 00:00:00

  • GAVI, the Vaccine Alliance.

    abstract::This year's Lasker-Bloomberg Public Service Award goes to GAVI, the Vaccine Alliance, for providing sustained access to childhood vaccines around the globe, saving millions of lives, and highlighting the power of immunization to prevent disease. ...


    pub_type: 历史文章,杂志文章


    authors: Zerhouni E

    更新日期:2019-09-19 00:00:00

  • Fast-Spiking Interneurons Supply Feedforward Control of Bursting, Calcium, and Plasticity for Efficient Learning.

    abstract::Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrop...


    pub_type: 杂志文章


    authors: Owen SF,Berke JD,Kreitzer AC

    更新日期:2018-02-08 00:00:00

  • Human beta-interferon gene expression is regulated by an inducible enhancer element.

    abstract::We have localized the regulatory sequence required for viral or poly(I)-poly(C) activation of human beta-interferon gene expression to a region located between -37 and -77 from the mRNA cap site. This sequence has the characteristics of an inducible enhancer element: it can act upstream or downstream of the beta-inter...


    pub_type: 杂志文章


    authors: Goodbourn S,Zinn K,Maniatis T

    更新日期:1985-06-01 00:00:00

  • Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures.

    abstract::A single mouse blastomere from an embryo until the 8-cell stage can generate an entire blastocyst. Whether laboratory-cultured cells retain a similar generative capacity remains unknown. Starting from a single stem cell type, extended pluripotent stem (EPS) cells, we established a 3D differentiation system that enable...


    pub_type: 杂志文章


    authors: Li R,Zhong C,Yu Y,Liu H,Sakurai M,Yu L,Min Z,Shi L,Wei Y,Takahashi Y,Liao HK,Qiao J,Deng H,Nuñez-Delicado E,Rodriguez Esteban C,Wu J,Izpisua Belmonte JC

    更新日期:2019-10-17 00:00:00

  • Recovery of S. cerevisiae a cells from G1 arrest by alpha factor pheromone requires endopeptidase action.

    abstract::Radioactive alpha factor is degraded to discrete biologically inactive fragments by the target a cells of S. cerevisiae, but not by alpha cells which make the pheromone. The pattern of cleavage products and sequence analysis of one fragment indicated that the first scission occurred between leucine 6 and lysine 7. The...


    pub_type: 杂志文章


    authors: Ciejek E,Thorner J

    更新日期:1979-11-01 00:00:00

  • A DNA-dependent protease involved in DNA-protein crosslink repair.

    abstract::Toxic DNA-protein crosslinks (DPCs) arise by ionizing irradiation and UV light, are particularly caused by endogenously produced reactive compounds such as formaldehyde, and also occur during compromised topoisomerase action. Although nucleotide excision repair and homologous recombination contribute to cell survival ...


    pub_type: 杂志文章


    authors: Stingele J,Schwarz MS,Bloemeke N,Wolf PG,Jentsch S

    更新日期:2014-07-17 00:00:00

  • Stabilizing HIF to Ameliorate Anemia.

    abstract::Erythropoietin (EPO) production in the kidney is regulated by the oxygen-sensing transcription factor HIF-1α, which is degraded under normoxic conditions by HIF-prolyl hydroxylase (HIF-PHD). Inhibition of HIF-PHD by roxadustat leads to increased EPO production, better iron absorption, and amelioration of anemia in chr...


    pub_type: 杂志文章


    authors: Voit RA,Sankaran VG

    更新日期:2020-01-09 00:00:00

  • Targeting of aberrant mRNAs to cytoplasmic processing bodies.

    abstract::In eukaryotes, a specialized pathway of mRNA degradation termed nonsense-mediated decay (NMD) functions in mRNA quality control by recognizing and degrading mRNAs with aberrant termination codons. We demonstrate that NMD in yeast targets premature termination codon (PTC)-containing mRNA to P-bodies. Upf1p is sufficien...


    pub_type: 杂志文章


    authors: Sheth U,Parker R

    更新日期:2006-06-16 00:00:00

  • Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices.

    abstract::The DNA-binding region of Myb consists of three imperfect tandem repeats (R1, R2, and R3). We have determined the solution structure of a specific DNA complex of the minimum DNA-binding domain (R2R3) by heteronuclear multidimensional NMR. Both R2 and R3 contain three helices, and the third helix in each is found to be...


    pub_type: 杂志文章


    authors: Ogata K,Morikawa S,Nakamura H,Sekikawa A,Inoue T,Kanai H,Sarai A,Ishii S,Nishimura Y

    更新日期:1994-11-18 00:00:00

  • Restriction sites containing CpG show a higher frequency of polymorphism in human DNA.

    abstract::Unique loci in the human genome were examined with restriction enzymes in order to detect restriction fragment length polymorphisms (RFLPs). Of 31 arbitrary loci, nine were detectably polymorphic, reflecting ten polymorphic restriction sites. Nine of the ten polymorphic sites were revealed with two restriction enzymes...


    pub_type: 杂志文章


    authors: Barker D,Schafer M,White R

    更新日期:1984-01-01 00:00:00

  • A STIMulus Package puts orai calcium channels to work.

    abstract::Activation of plasma membrane calcium channels by depletion of endoplasmic reticulum (ER) calcium stores is important for calcium entry in many cell types. Park et al. (2009) now show that direct binding of the ER protein STIM to tetramers of the Orai1 calcium channel in the plasma membrane triggers opening of this ch...


    pub_type: 评论,社论


    authors: Clapham DE

    更新日期:2009-03-06 00:00:00

  • Oncogenic Signaling Pathways in The Cancer Genome Atlas.

    abstract::Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expressio...


    pub_type: 杂志文章


    authors: Sanchez-Vega F,Mina M,Armenia J,Chatila WK,Luna A,La KC,Dimitriadoy S,Liu DL,Kantheti HS,Saghafinia S,Chakravarty D,Daian F,Gao Q,Bailey MH,Liang WW,Foltz SM,Shmulevich I,Ding L,Heins Z,Ochoa A,Gross B,Gao J,Z

    更新日期:2018-04-05 00:00:00

  • Location of the cell-attachment site in fibronectin with monoclonal antibodies and proteolytic fragments of the molecule.

    abstract::Proteolytic fragments of human plasma fibronectin were used to identify monoclonal antibodies reacting with the various domains of fibronectin. One of these antibodies, which reacts with cell-attachment-promoting fragments of fibronectin, inhibits attachment of cells to fibronectin-coated surfaces. A cell-attachment-p...


    pub_type: 杂志文章


    authors: Pierschbacher MD,Hayman EG,Ruoslahti E

    更新日期:1981-10-01 00:00:00

  • In Praise of Descriptive Science: A Breath of Fresh AIRE.

    abstract::Meyer et al. find that subjects lacking the AIRE gene, critical for self-tolerance in T lymphocytes, show a broad range of autoantibody specificities, which can have extremely high affinities. The data also suggest that some of these autoantibodies can, surprisingly, prevent some types of autoimmunity, particularly ty...


    pub_type: 评论,杂志文章


    authors: Davis MM

    更新日期:2016-07-28 00:00:00

  • A Single Transcription Factor Drives Toxoplasma gondii Differentiation.

    abstract::Microbes that cause persistent infections (e.g., herpes viruses) do so by switching from fast-growing lytic states to slow-growing latent states. Waldman et al. have identified a single transcription factor that governs the switch between the lytic and latent forms of Toxoplasma gondii, a parasite that causes a persis...


    pub_type: 评论,杂志文章


    authors: Kochanowsky JA,Koshy AA

    更新日期:2020-01-23 00:00:00

  • Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans.

    abstract::The sulfated glycosaminoglycan, heparin, was found to release 125I-labeled low density lipoprotein (125I-LDL) from its receptor site on the surface of normal human fibroblasts. Measurement of the amount of 125I-LDL released by heparin permitted the resolution of the total cellular uptake of 125I-LDL at 37 degrees C in...


    pub_type: 杂志文章


    authors: Goldstein JL,Basu SK,Brunschede GY,Brown MS

    更新日期:1976-01-01 00:00:00