Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle.

Abstract:

:Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). By combining PGC-1alpha-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor alpha (Erralpha) and GA repeat-binding protein alpha as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1alpha-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Erralpha and GA-binding protein a partner with PGC-1alpha in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Erralpha, we demonstrated its key role in PGC-1alpha-mediated effects on gene regulation and cellular respiration. These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1alpha action in the OXPHOS pathway, and suggest that Erralpha agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus.

authors

Mootha VK,Handschin C,Arlow D,Xie X,St Pierre J,Sihag S,Yang W,Altshuler D,Puigserver P,Patterson N,Willy PJ,Schulman IG,Heyman RA,Lander ES,Spiegelman BM

doi

10.1073/pnas.0401401101

keywords:

subject

Has Abstract

pub_date

2004-04-27 00:00:00

pages

6570-5

issue

17

eissn

0027-8424

issn

1091-6490

pii

0401401101

journal_volume

101

pub_type

杂志文章
  • Protein tyrosine phosphorylation in synaptic vesicles.

    abstract::Protein tyrosine phosphorylation in purified synaptic vesicles from rat forebrain has been studied in the presence of Mn2+ and orthovanadate. High levels of endogenous protein tyrosine phosphorylation were observed. Four major phosphoproteins, with apparent molecular masses of 105, 94, 38, and 30 kDa, were shown to co...

    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.85.3.762

    authors: Pang DT,Wang JK,Valtorta F,Benfenati F,Greengard P

    更新日期:1988-02-01 00:00:00

  • Efficiency of truncation selection.

    abstract::Truncation selection is known to be the most efficient form of directional selection. When this is modified so that the fitness increases linearly over a range of one or two standard deviations of the value of the selected character, the efficiency is reduced, but not greatly. When truncation selection is compared to ...

    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.76.1.396

    authors: Crow JF,Kimura M

    更新日期:1979-01-01 00:00:00

  • Harmonic dynamics of the abelian sandpile.

    abstract::The abelian sandpile is a cellular automaton which serves as the archetypical model to study self-organized criticality, a phenomenon occurring in various biological, physical, and social processes. Its recurrent configurations form an abelian group, whose identity is a fractal composed of self-similar patches. Here, ...

    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.1812015116

    authors: Lang M,Shkolnikov M

    更新日期:2019-02-19 00:00:00

  • Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: outcome with influenza A virus is unique.

    abstract::We examine the IFN-alpha/beta-independent activation of cellular transcription that constitutes an early antiviral response of cells against influenza A and B viruses, which cause widespread epidemics in humans. We show that influenza B virus induces the synthesis in human cells of several mature mRNAs encoded by gene...

    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.152327499

    authors: Kim MJ,Latham AG,Krug RM

    更新日期:2002-07-23 00:00:00

  • Methyltransferases of gentamicin biosynthesis.

    abstract::Gentamicin C complex from Micromonospora echinospora remains a globally important antibiotic, and there is revived interest in the semisynthesis of analogs that might show improved therapeutic properties. The complex consists of five components differing in their methylation pattern at one or more sites in the molecul...

    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.1711603115

    authors: Li S,Guo J,Reva A,Huang F,Xiong B,Liu Y,Deng Z,Leadlay PF,Sun Y

    更新日期:2018-02-06 00:00:00

  • Therapeutic targeting of tumor-associated myeloid cells synergizes with radiation therapy for glioblastoma.

    abstract::Tumor-associated myeloid cells (TAMCs) are key drivers of immunosuppression in the tumor microenvironment, which profoundly impedes the clinical response to immune-dependent and conventional therapeutic modalities. As a hallmark of glioblastoma (GBM), TAMCs are massively recruited to reach up to 50% of the brain tumor...

    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.1906346116

    authors: Zhang P,Miska J,Lee-Chang C,Rashidi A,Panek WK,An S,Zannikou M,Lopez-Rosas A,Han Y,Xiao T,Pituch KC,Kanojia D,Balyasnikova IV,Lesniak MS

    更新日期:2019-11-19 00:00:00

  • Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity.

    abstract::The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how...

    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.0901023106

    authors: Miller LM,Recanzone GH

    更新日期:2009-04-07 00:00:00

  • Dual origin of mesenchymal stem cells contributing to organ growth and repair.

    abstract::In many adult tissues, mesenchymal stem cells (MSCs) are closely associated with perivascular niches and coexpress many markers in common with pericytes. The ability of pericytes to act as MSCs, however, remains controversial. By using genetic lineage tracing, we show that some pericytes differentiate into specialized...

    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.1015449108

    authors: Feng J,Mantesso A,De Bari C,Nishiyama A,Sharpe PT

    更新日期:2011-04-19 00:00:00

  • Modification of ghrelin receptor signaling by somatostatin receptor-5 regulates insulin release.

    abstract::Both ghrelin and somatostatin (SST) inhibit glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells, but how these independent actions are regulated has been unclear. The mechanism must accommodate noncanonical ghrelin receptor (GHS-R1a)-G-protein coupling to Gα(i/o) instead of Gα(q11) and dependence on en...

    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.1209590109

    authors: Park S,Jiang H,Zhang H,Smith RG

    更新日期:2012-11-13 00:00:00

  • Stimulation of the expression of osteogenic and chondrogenic phenotypes in vitro by osteogenin.

    abstract::Osteogenin was recently purified and the amino acid sequences of tryptic peptides were determined. Osteogenin in conjunction with insoluble collagenous bone matrix induces cartilage and bone formation in vivo. To understand the mechanism of action of osteogenin, we examined its influence on periosteal cells, osteoblas...

    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.86.22.8793

    authors: Vukicevic S,Luyten FP,Reddi AH

    更新日期:1989-11-01 00:00:00

  • The novel PII-interactor PirC identifies phosphoglycerate mutase as key control point of carbon storage metabolism in cyanobacteria.

    abstract::Nitrogen limitation imposes a major transition in the lifestyle of nondiazotrophic cyanobacteria that is controlled by a complex interplay of regulatory factors involving the pervasive signal processor PII Immediately upon nitrogen limitation, newly fixed carbon is redirected toward glycogen synthesis. How the metabol...

    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.2019988118

    authors: Orthwein T,Scholl J,Spät P,Lucius S,Koch M,Macek B,Hagemann M,Forchhammer K

    更新日期:2021-02-09 00:00:00

  • Folding free energy function selects native-like protein sequences in the core but not on the surface.

    abstract::An automatic protein design procedure is used to select amino acid sequences that optimize the folding free energy function for a given protein. The only information used in designing the sequences is a set of known backbone structures for each protein, a rotamer library, and a well established classical empirical for...

    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.212068599

    authors: Jaramillo A,Wernisch L,Héry S,Wodak SJ

    更新日期:2002-10-15 00:00:00

  • Insect feeding mobilizes a unique plant defense protease that disrupts the peritrophic matrix of caterpillars.

    abstract::Plants frequently respond to herbivorous insect attack by synthesizing defense proteins that deter insect feeding and prevent additional herbivory. Maize (Zea mays L.) lines, resistant to feeding by a number of lepidopteran species, rapidly mobilize a unique 33-kDa cysteine protease in response to caterpillar feeding....

    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.202224899

    authors: Pechan T,Cohen A,Williams WP,Luthe DS

    更新日期:2002-10-01 00:00:00

  • T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells.

    abstract::IFN-gamma is well known as the signature cytokine of CD4+ T helper 1, CD8+, and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that controls IFN-gamma exp...

    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.1332767100

    authors: Lugo-Villarino G,Maldonado-Lopez R,Possemato R,Penaranda C,Glimcher LH

    更新日期:2003-06-24 00:00:00

  • Unprecedented pathway of reducing equivalents in a diflavin-linked disulfide oxidoreductase.

    abstract::Flavoproteins participate in a wide variety of physiologically relevant processes that typically involve redox reactions. Within this protein superfamily, there exists a group that is able to transfer reducing equivalents from FAD to a redox-active disulfide bridge, which further reduces disulfide bridges in target pr...

    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.1713698114

    authors: Buey RM,Arellano JB,López-Maury L,Galindo-Trigo S,Velázquez-Campoy A,Revuelta JL,de Pereda JM,Florencio FJ,Schürmann P,Buchanan BB,Balsera M

    更新日期:2017-11-28 00:00:00

  • Ionizing radiation and tritium transmutation both cause formation of 5-hydroxymethyl-2'-deoxyuridine in cellular DNA.

    abstract::HeLa cells grown in the presence of [methyl-3H]thymidine contained large amounts of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in their DNA. When the cells were grown in [6-3H]thymidine and their DNA was labeled to the same specific activity, no HMdU was present. When such [6-3H]thymidine-labeled cells were exposed to inc...

    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.81.2.318

    authors: Teebor GW,Frenkel K,Goldstein MS

    更新日期:1984-01-01 00:00:00

  • Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen.

    abstract::A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the form...

    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.74.11.4777

    authors: Chance B,Leigh JS Jr

    更新日期:1977-11-01 00:00:00

  • Juvenile hormone receptors in insect larval epidermis: identification by photoaffinity labeling.

    abstract::Tritiated photoaffinity analogs of the natural lepidopteran juvenile hormones, JH I and II [epoxy[3H]bishomofarnesyl diazoacetate ([3H]EBDA) and epoxy[3H]homofarnesyl diazoacetate ([3H]EHDA)], and of the JH analog methoprene [[3H]methoprene diazoketone ([3H]MDK)] were synthesized and used to identify specific JH bindi...

    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.87.2.796

    authors: Palli SR,Osir EO,Eng W,Boehm MF,Edwards M,Kulcsar P,Ujvary I,Hiruma K,Prestwich GD,Riddiford LM

    更新日期:1990-01-01 00:00:00

  • Processing of the 5' end of Escherichia coli 16S ribosomal RNA.

    abstract::We have isolated and partially characterized an endonuclease involved in processing the 5' end of 16S rRNA of Escherichia coli. A mutant strain that is deficient in this enzyme accumulates a new precursor of 16S rRNA, named 16.3S rRNA. This rRNA has the 3' end of mature 16S rRNA but is about 60 nucleotides longer at t...

    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.75.8.3598

    authors: Dahlberg AE,Dahlberg JE,Lund E,Tokimatsu H,Rabson AB,Calvert PC,Reynolds F,Zahalak M

    更新日期:1978-08-01 00:00:00

  • 7alpha-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system.

    abstract::It is becoming clear that steroids can be synthesized de novo by the brain and other nervous systems. Such steroids are called neurosteroids, and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. In this study, we show that the newt brain actively produces 7alpha-hydroxypregne...

    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.0407176101

    authors: Matsunaga M,Ukena K,Baulieu EE,Tsutsui K

    更新日期:2004-12-07 00:00:00

  • A splicing variant of a death domain protein that is regulated by a mitogen-activated kinase is a substrate for c-Jun N-terminal kinase in the human central nervous system.

    abstract::The mitogen-activated kinase activating death domain protein (MADD) that is differentially expressed in neoplastic vs. normal cells (DENN) was identified as a substrate for c-Jun N-terminal kinase 3, the first demonstration of such an activity for this stress-activated kinase that is predominantly expressed in the bra...

    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.95.5.2586

    authors: Zhang Y,Zhou L,Miller CA

    更新日期:1998-03-03 00:00:00

  • Convergent and parallel activation of low-conductance potassium channels by calcium and cAMP-dependent protein kinase.

    abstract::K+ channels, which have been linked to regulation of electrogenic solute transport as well as Ca2+ influx, represent a locus in hepatocytes for the concerted actions of hormones that employ Ca2+ and cAMP as intracellular messengers. Despite considerable study, the single-channel basis for synergistic effects of Ca2+ a...

    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.92.15.7115

    authors: Lidofsky SD

    更新日期:1995-07-18 00:00:00

  • High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice.

    abstract::To permit rapid optical control of brain activity, we have engineered multiple lines of transgenic mice that express the light-activated cation channel Channelrhodopsin-2 (ChR2) in subsets of neurons. Illumination of ChR2-positive neurons in brain slices produced photocurrents that generated action potentials within m...

    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.0700384104

    authors: Wang H,Peca J,Matsuzaki M,Matsuzaki K,Noguchi J,Qiu L,Wang D,Zhang F,Boyden E,Deisseroth K,Kasai H,Hall WC,Feng G,Augustine GJ

    更新日期:2007-05-08 00:00:00

  • On the law of the iterated logarithm.

    abstract::The law of the iterated logarithm provides a family of bounds all of the same order such that with probability one only finitely many partial sums of a sequence of independent and identically distributed random variables exceed some members of the family, while for others infinitely many do so. In the former case, the...

    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.63.2.289

    authors: Slivka J

    更新日期:1969-06-01 00:00:00

  • Executioner caspase-3 and caspase-7 are functionally distinct proteases.

    abstract::Members of the caspase family of cysteine proteases play central roles in coordinating the stereotypical events that occur during apoptosis. Because the major executioner caspases, caspase-3 and caspase-7, exhibit almost indistinguishable activity toward certain synthetic peptide substrates, this has led to the widesp...

    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.0707715105

    authors: Walsh JG,Cullen SP,Sheridan C,Lüthi AU,Gerner C,Martin SJ

    更新日期:2008-09-02 00:00:00

  • Selfish supernumerary chromosome reveals its origin as a mosaic of host genome and organellar sequences.

    abstract::Supernumerary B chromosomes are optional additions to the basic set of A chromosomes, and occur in all eukaryotic groups. They differ from the basic complement in morphology, pairing behavior, and inheritance and are not required for normal growth and development. The current view is that B chromosomes are parasitic e...

    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.1204237109

    authors: Martis MM,Klemme S,Banaei-Moghaddam AM,Blattner FR,Macas J,Schmutzer T,Scholz U,Gundlach H,Wicker T,Šimková H,Novák P,Neumann P,Kubaláková M,Bauer E,Haseneyer G,Fuchs J,Doležel J,Stein N,Mayer KF,Houben A

    更新日期:2012-08-14 00:00:00

  • Endonuclease S1-sensitive site in chicken pro-alpha 2(I) collagen 5' flanking gene region.

    abstract::A site that is preferentially cleaved by the single-strand-specific endonuclease from Aspergillus oryzae was located in vitro 180 base pairs upstream from the 5' end of the chicken pro-alpha 2(I) collagen gene. It is found in supercoiled plasmids with a negative superhelical density of -0.024 or more but not in linear...

    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.81.6.1659

    authors: Finer MH,Fodor EJ,Boedtker H,Doty P

    更新日期:1984-03-01 00:00:00

  • Microangiectasias: structural regulators of lymphocyte transmigration.

    abstract::The migration of lymphocytes into inflammatory tissue requires the migrating cell to overcome mechanical forces produced by blood flow. A generally accepted hypothesis is that these forces are overcome by a multistep sequence of adhesive interactions between lymphocytes and endothelial cells. This hypothesis has been ...

    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.1232173100

    authors: Secomb TW,Konerding MA,West CA,Su M,Young AJ,Mentzer SJ

    更新日期:2003-06-10 00:00:00

  • Nonmuscle myosin II exerts tension but does not translocate actin in vertebrate cytokinesis.

    abstract::During vertebrate cytokinesis it is thought that contractile ring constriction is driven by nonmuscle myosin II (NM II) translocation of antiparallel actin filaments. Here we report in situ, in vitro, and in vivo observations that challenge this hypothesis. Graded knockdown of NM II in cultured COS-7 cells reveals tha...

    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.1116268109

    authors: Ma X,Kovács M,Conti MA,Wang A,Zhang Y,Sellers JR,Adelstein RS

    更新日期:2012-03-20 00:00:00

  • Relational representation in the olfactory system.

    abstract::The perceptual quality of odors usually is robust to variability in concentration. However, maps of neural activation across the olfactory bulb glomerular layer are not stable in this respect; rather, glomerular odor representations both broaden and intensify as odorant concentrations are increased. The relative level...

    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.0608564104

    authors: Cleland TA,Johnson BA,Leon M,Linster C

    更新日期:2007-02-06 00:00:00