Phosphatidic acid mediates demyelination in Lpin1 mutant mice.


:Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order to study the role of lipid metabolism in myelinating glial cells, we specifically deleted in Schwann cells the Lpin1 gene, which encodes the Mg2+-dependent phosphatidate phosphatase (PAP1) enzyme necessary for normal triacylglycerol biosynthesis. The affected animals developed pronounced peripheral neuropathy characterized by myelin degradation, Schwann cell dedifferentiation and proliferation, and a reduction in nerve conduction velocity. The observed demyelination is mediated by endoneurial accumulation of the substrate of the PAP1 enzyme, phosphatidic acid (PA). In addition, we show that PA is a potent activator of the MEK-Erk pathway in Schwann cells, and that this activation is required for PA-induced demyelination. Our results therefore reveal a surprising role for PA in Schwann cell fate determination and provide evidence of a direct link between diseases affecting lipid metabolism and abnormal Schwann cell function.


Genes Dev


Genes & development


Nadra K,de Preux Charles AS,Médard JJ,Hendriks WT,Han GS,Grès S,Carman GM,Saulnier-Blache JS,Verheijen MH,Chrast R




Has Abstract


2008-06-15 00:00:00














  • Functional domains of the yeast transcription/replication factor MCM1.

    abstract::MCM1 is an essential yeast DNA-binding protein that affects both minichromosome maintenance, in a manner suggesting that it has DNA replication initiation function, and gene expression. It activates alpha-specific genes together with MAT alpha 1, and represses a-specific genes together with MAT alpha 2. Alone, MCM1 ca...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Christ C,Tye BK

    更新日期:1991-05-01 00:00:00

  • Regulating the regulator: an RNA decoy acts as an OFF switch for the regulation of an sRNA.

    abstract::Many bacterial small regulatory RNAs (sRNAs) pair with mRNA targets, stimulating or inhibiting mRNA stability and/or translation. Regulation of these sRNAs is usually due to tight transcriptional regulation of synthesis.In this issue of Genes & Development and a related paper in Molecular Microbiology, Figueroa-Bossi ...

    journal_title:Genes & development

    pub_type: 评论,杂志文章


    authors: Mandin P,Gottesman S

    更新日期:2009-09-01 00:00:00

  • Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.

    abstract::Myxococcus xanthus development requires CsgA, a member of the short-chain alcohol dehydrogenase (SCAD) family of proteins. We show that CsgA and SocA, a protein that can replace CsgA function in vivo, oxidize the 2'-OH glycerol moiety on cardiolipin and phosphatidylglycerol to produce diacylglycerol (DAG), dihydroxyac...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Boynton TO,Shimkets LJ

    更新日期:2015-09-15 00:00:00

  • The global transcriptional regulators, SSN6 and TUP1, play distinct roles in the establishment of a repressive chromatin structure.

    abstract::Repression of a-cell specific gene expression in yeast alpha cells requires MAT alpha 2 and MCM1, as well as two global repressors, SSN6 and TUP1. Previous studies demonstrated that nucleosomes positioned adjacent to the alpha 2/MCM1 operator in alpha cells directly contribute to repression. To investigate the possibi...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Cooper JP,Roth SY,Simpson RT

    更新日期:1994-06-15 00:00:00

  • 3' end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells.

    abstract::3' end formation of pre-mRNAs is coupled to their transcription via the C-terminal domain (CTD) of RNA polymerase II (Pol II). Nearly all protein-coding transcripts are matured by cleavage and polyadenylation (CPA), which is frequently misregulated in disease. Understanding how transcription is coordinated with CPA in...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Davidson L,Muniz L,West S

    更新日期:2014-02-15 00:00:00

  • Mismatch repair-dependent processing of methylation damage gives rise to persistent single-stranded gaps in newly replicated DNA.

    abstract::O(6)-Methylguanine ((Me)G) is a highly cytotoxic DNA modification generated by S(N)1-type methylating agents. Despite numerous studies implicating DNA replication, mismatch repair (MMR), and homologous recombination (HR) in (Me)G toxicity, its mode of action has remained elusive. We studied the molecular transactions ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Mojas N,Lopes M,Jiricny J

    更新日期:2007-12-15 00:00:00

  • DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.

    abstract::Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Sansam CL,Shepard JL,Lai K,Ianari A,Danielian PS,Amsterdam A,Hopkins N,Lees JA

    更新日期:2006-11-15 00:00:00

  • Deficient mismatch repair improves organismal fitness and survival of mice with dysfunctional telomeres.

    abstract::Mismatch repair (MMR) has important roles in meiotic and mitotic recombination, DNA damage signaling, and various aspects of DNA metabolism including class-switch recombination, somatic hypermutation, and triplet-repeat expansion. Defects in MMR are responsible for human cancers characterized by microsatellite instabi...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Siegl-Cachedenier I,Muñoz P,Flores JM,Klatt P,Blasco MA

    更新日期:2007-09-01 00:00:00

  • Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells.

    abstract::In murine plasmacytoma and human Burkitt's lymphoma cells, one allele of c-myc is translocated into one of the immunoglobulin loci, resulting in a characteristic pattern of deregulated c-myc transcription. Translocation events between c-myc and the IgH locus segregate c-myc and the IgH intron enhancer to different rec...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Madisen L,Groudine M

    更新日期:1994-09-15 00:00:00

  • Specificity of single LIM motifs in targeting and LIM/LIM interactions in situ.

    abstract::The LIM motif defines a double zinc finger structure found in proteins involved in cell fate determination and growth control. LIM proteins, which include LIM homeo domain, LIM kinase, focal adhesion, and LIM-only proteins, usually contain two or more LIM motifs clustered at their amino- or carboxy-terminal end. At pr...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Arber S,Caroni P

    更新日期:1996-02-01 00:00:00

  • Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos.

    abstract::The secreted Drosophila Hedgehog (Hh) protein induces transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci). Protein kinase A (PKA) has been implicated in the mechanism of Hh signal transduction ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Ohlmeyer JT,Kalderon D

    更新日期:1997-09-01 00:00:00

  • The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.

    abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kobayashi T,Mizuno H,Imayoshi I,Furusawa C,Shirahige K,Kageyama R

    更新日期:2009-08-15 00:00:00

  • Radical mutations reveal TATA-box binding protein surfaces required for activated transcription in vivo.

    abstract::Regions on the surface of human TATA-box binding protein (TBP) required for activated transcription in vivo were defined by construction of a library of 89 surface residue mutants with radical substitutions that were assayed for their ability to support activated transcription in vivo, basal transcription in vitro, an...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Bryant GO,Martel LS,Burley SK,Berk AJ

    更新日期:1996-10-01 00:00:00

  • Localized surface activity of torso, a receptor tyrosine kinase, specifies terminal body pattern in Drosophila.

    abstract::The subdivision of the Drosophila body into distinct terminal and central domains depends on the torso (tor) protein, a putative receptor tyrosine kinase that is active at both ends of the early embryo. We show that the tor protein is uniformly expressed along the surface membrane of early embryos despite its localize...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Casanova J,Struhl G

    更新日期:1989-12-01 00:00:00

  • Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine.

    abstract::Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activitie...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Cheung EC,Lee P,Ceteci F,Nixon C,Blyth K,Sansom OJ,Vousden KH

    更新日期:2016-01-01 00:00:00

  • Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4.

    abstract::Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Zhang X,Ozawa Y,Lee H,Wen YD,Tan TH,Wadzinski BE,Seto E

    更新日期:2005-04-01 00:00:00

  • DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly.

    abstract::In the absence of growth signals, cells exit the cell cycle and enter into G0 or quiescence. Alternatively, cells enter senescence in response to inappropriate growth signals such as oncogene expression. The molecular mechanisms required for cell cycle exit into quiescence or senescence are poorly understood. The DREA...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Litovchick L,Florens LA,Swanson SK,Washburn MP,DeCaprio JA

    更新日期:2011-04-15 00:00:00

  • Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.

    abstract::Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 a...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Wagner AJ,Kokontis JM,Hay N

    更新日期:1994-12-01 00:00:00

  • Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in Drosophila.

    abstract::To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slow...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Khodor YL,Rodriguez J,Abruzzi KC,Tang CH,Marr MT 2nd,Rosbash M

    更新日期:2011-12-01 00:00:00

  • Checkpoint activation regulates mutagenic translesion synthesis.

    abstract::Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replica...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kai M,Wang TS

    更新日期:2003-01-01 00:00:00

  • PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family.

    abstract::The p53 tumor suppressor activates either cell cycle arrest or apoptosis in response to cellular stress. Mouse embryo fibroblasts (MEFs) provide a powerful primary cell system to study both p53-dependent pathways. Specifically, in response to DNA damage, MEFs undergo p53-dependent G(1) arrest, whereas MEFs expressing ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Attardi LD,Reczek EE,Cosmas C,Demicco EG,McCurrach ME,Lowe SW,Jacks T

    更新日期:2000-03-15 00:00:00

  • Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break.

    abstract::The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interacti...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Anderson CM,Korkin D,Smith DL,Makovets S,Seidel JJ,Sali A,Blackburn EH

    更新日期:2008-04-01 00:00:00

  • Inactivation of AtRac1 by abscisic acid is essential for stomatal closure.

    abstract::Plant water homeostasis is maintained by the phytohormone abscisic acid (ABA), which triggers stomatal pore closure in response to drought stress. We identified the Arabidopsis small guanosine triphosphatase (GTPase) protein AtRac1 as a central component in the ABA-mediated stomatal closure process. ABA treatment indu...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Lemichez E,Wu Y,Sanchez JP,Mettouchi A,Mathur J,Chua NH

    更新日期:2001-07-15 00:00:00

  • Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo.

    abstract::Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to dem...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Wang L,Liu L,Berger SL

    更新日期:1998-03-01 00:00:00

  • A nonproteolytic function of the proteasome is required for the dissociation of Cdc2 and cyclin B at the end of M phase.

    abstract::Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that re...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Nishiyama A,Tachibana K,Igarashi Y,Yasuda H,Tanahashi N,Tanaka K,Ohsumi K,Kishimoto T

    更新日期:2000-09-15 00:00:00

  • The Arabidopsis BODENLOS gene encodes an auxin response protein inhibiting MONOPTEROS-mediated embryo patterning.

    abstract::Developmental responses to the plant hormone auxin are thought to be mediated by interacting pairs from two protein families: short-lived inhibitory IAA proteins and ARF transcription factors binding to auxin-response elements. monopteros mutants lacking activating ARF5 and the auxin-insensitive mutant bodenlos fail t...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Hamann T,Benkova E,Bäurle I,Kientz M,Jürgens G

    更新日期:2002-07-01 00:00:00

  • Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition.

    abstract::The widespread class of RNA viruses that utilize internal ribosome entry sites (IRESs) for translation include poliovirus and Hepatitis C virus. To identify host factors required for IRES-dependent translation and viral replication, we performed a genome-wide RNAi screen in Drosophila cells infected with Drosophila C ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Cherry S,Doukas T,Armknecht S,Whelan S,Wang H,Sarnow P,Perrimon N

    更新日期:2005-02-15 00:00:00

  • Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.

    abstract::Expression of HNF-4, a transcription factor in the steroid hormone receptor superfamily, is detected only in the visceral endoderm of mouse embryos during gastrulation and is expressed in certain embryonic tissues from 8.5 days of gestation. To examine the role of HNF-4 during embryonic development, we disrupted the g...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Chen WS,Manova K,Weinstein DC,Duncan SA,Plump AS,Prezioso VR,Bachvarova RF,Darnell JE Jr

    更新日期:1994-10-15 00:00:00

  • Skp2-dependent degradation of p27kip1 is essential for cell cycle progression.

    abstract::The activity of the SCF(skp2) E3 ligase is required for the proteolytic turnover of several proteins involved in cell cycle control and transcriptional regulation. Loss of skp2 in the mouse leads to a complex phenotype including changes in cell size and DNA content as well as severe proliferation defects. Here we show...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kossatz U,Dietrich N,Zender L,Buer J,Manns MP,Malek NP

    更新日期:2004-11-01 00:00:00

  • A physiological role for gene loops in yeast.

    abstract::DNA loops that juxtapose the promoter and terminator regions of RNA polymerase II-transcribed genes have been identified in yeast and mammalian cells. Loop formation is transcription-dependent and requires components of the pre-mRNA 3'-end processing machinery. Here we report that looping at the yeast GAL10 gene persi...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Lainé JP,Singh BN,Krishnamurthy S,Hampsey M

    更新日期:2009-11-15 00:00:00