The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases.

Abstract:

:Homologs of the chromatin-bound yeast silent information regulator 2 (SIR2) protein are found in organisms from all biological kingdoms. SIR2 itself was originally discovered to influence mating-type control in haploid cells by locus-specific transcriptional silencing. Since then, SIR2 and its homologs have been suggested to play additional roles in suppression of recombination, chromosomal stability, metabolic regulation, meiosis, and aging. Considering the far-ranging nature of these functions, a major experimental goal has been to understand the molecular mechanism(s) by which this family of proteins acts. We report here that members of the SIR2 family catalyze an NAD-nicotinamide exchange reaction that requires the presence of acetylated lysines such as those found in the N termini of histones. Significantly, these enzymes also catalyze histone deacetylation in a reaction that absolutely requires NAD, thereby distinguishing them from previously characterized deacetylases. The enzymes are active on histone substrates that have been acetylated by both chromatin assembly-linked and transcription-related acetyltransferases. Contrary to a recent report, we find no evidence that these proteins ADP-ribosylate histones. Discovery of an intrinsic deacetylation activity for the conserved SIR2 family provides a mechanism for modifying histones and other proteins to regulate transcription and diverse biological processes.

authors

Landry J,Sutton A,Tafrov ST,Heller RC,Stebbins J,Pillus L,Sternglanz R

doi

10.1073/pnas.110148297

keywords:

subject

Has Abstract

pub_date

2000-05-23 00:00:00

pages

5807-11

issue

11

eissn

0027-8424

issn

1091-6490

pii

110148297

journal_volume

97

pub_type

杂志文章
  • Isolation of two alleles of the b locus of Ustilago maydis.

    abstract::The basidiomycete Ustilago maydis is the causative agent of the disease corn smut. To be pathogenic, strains of U. maydis must be heterozygous for a locus called "b," which appears to control both pathogenicity and sexual development. Two alleles of the b locus of U. maydis were isolated by complementation and hybridi...

    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.86.3.978

    authors: Kronstad JW,Leong SA

    更新日期:1989-02-01 00:00:00

  • alpha-latrotoxin of black widow spider venom depolarizes the plasma membrane, induces massive calcium influx, and stimulates transmitter release in guinea pig brain synaptosomes.

    abstract::The effect of alpha-latrotoxin from black widow spider venom upon guinea pig cerebral cortical synaptosomes is described. Plasma membrane potential (delta psi p), in situ mitochondrial membrane potential (delta psi m), Ca2+ transport, gamma-amino[3H]butyrate release, [3H]noradrenaline release, and synaptosomal ATP wer...

    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.79.24.7924

    authors: Nicholls DG,Rugolo M,Scott IG,Meldolesi J

    更新日期:1982-12-01 00:00:00

  • RHL1 is an essential component of the plant DNA topoisomerase VI complex and is required for ploidy-dependent cell growth.

    abstract::How cells achieve their final sizes is a pervasive biological question. One strategy to increase cell size is for the cell to amplify its chromosomal DNA content through endoreduplication cycles. Although endoreduplication is widespread in eukaryotes, we know very little about its molecular mechanisms. Successful prog...

    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.0505883102

    authors: Sugimoto-Shirasu K,Roberts GR,Stacey NJ,McCann MC,Maxwell A,Roberts K

    更新日期:2005-12-20 00:00:00

  • Identification of differential translation in genome wide studies.

    abstract::Regulation of gene expression through translational control is a fundamental mechanism implicated in many biological processes ranging from memory formation to innate immunity and whose dysregulation contributes to human diseases. Genome wide analyses of translational control strive to identify differential translatio...

    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.1006821107

    authors: Larsson O,Sonenberg N,Nadon R

    更新日期:2010-12-14 00:00:00

  • Actin stress in cell reprogramming.

    abstract::Cell mechanics plays a role in stem cell reprogramming and differentiation. To understand this process better, we created a genetically encoded optical probe, named actin-cpstFRET-actin (AcpA), to report forces in actin in living cells in real time. We showed that stemness was associated with increased force in actin....

    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.1411683111

    authors: Guo J,Wang Y,Sachs F,Meng F

    更新日期:2014-12-09 00:00:00

  • COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans.

    abstract::Two-component histidine kinases recently have been found in eukaryotic organisms including fungi, slime molds, and plants. We describe the identification of a gene, COS1, from the opportunistic pathogen Candida albicans by using a PCR-based screening strategy. The sequence of COS1 indicates that it encodes a homolog 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.95.12.7069

    authors: Alex LA,Korch C,Selitrennikoff CP,Simon MI

    更新日期:1998-06-09 00:00:00

  • A long-range regulatory element of Hoxc8 identified by using the pClasper vector.

    abstract::Hox genes are located in highly conserved clusters. The significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other Hox genes. This hypothesis is supported by studies on several Hox genes in which even larg...

    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.93.6.2426

    authors: Bradshaw MS,Shashikant CS,Belting HG,Bollekens JA,Ruddle FH

    更新日期:1996-03-19 00:00:00

  • Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase by autophosphorylation: ATP modulates production of an autonomous enzyme.

    abstract::The multifunctional Ca2+/calmodulin-dependent protein kinase purified from rat brain cytosol undergoes an intramolecular self-phosphorylation or autophosphorylation. Autophosphorylation produces two strikingly different effects on kinase activity that are dependent on the level of ATP used in the reaction. At low but ...

    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.83.24.9497

    authors: Lou LL,Lloyd SJ,Schulman H

    更新日期:1986-12-01 00:00:00

  • Nucleotide sequencing of DNA: preliminary characterization of the products of specific cleavages at guanine, cytosine, or adenine residues (bacteriophage M13-ribosubstitution-DNA polymerase I-electrophoresis-two-dimensional fingerprinting).

    abstract::DNA synthesized in vitro from a phage M13 template has been cleaved at either guanine, adenine, or cytosine residues by ribosubstitution techniques. Fingerprints of the fragments obtained suggest that DNA sequencing will be possible with this technique. ...

    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.69.1.238

    authors: Salser W,Fry K,Brunk C,Poon R

    更新日期:1972-01-01 00:00:00

  • Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility.

    abstract::Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid in...

    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.2010133117

    authors: Lu Y,Sandoval A,Voss S,Lai Z,Kneitz S,Boswell W,Boswell M,Savage M,Walter C,Warren W,Schartl M,Walter R

    更新日期:2020-11-24 00:00:00

  • Two-fluid theory and thermodynamic properties of liquid mixtures. Application to hard-sphere mixtures.

    abstract::This paper is the second of three describing a two-fluid theory of binary liquid mixtures. The general theory presented in the preceding paper is used to derive a model for calculating thermodynamic properties of hard-sphere mixtures. Calculations indicate that desirable boundary conditions are satisfied. ...

    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.79.16.5103

    authors: Brandani V,Prausnitz JM

    更新日期:1982-08-01 00:00:00

  • Trifunctional lipid probes for comprehensive studies of single lipid species in living cells.

    abstract::Lipid-mediated signaling events regulate many cellular processes. Investigations of the complex underlying mechanisms are difficult because several different methods need to be used under varying conditions. Here we introduce multifunctional lipid derivatives to study lipid metabolism, lipid-protein interactions, and ...

    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.1611096114

    authors: Höglinger D,Nadler A,Haberkant P,Kirkpatrick J,Schifferer M,Stein F,Hauke S,Porter FD,Schultz C

    更新日期:2017-02-14 00:00:00

  • Indian annual ambient air quality standard is achievable by completely mitigating emissions from household sources.

    abstract::Exposures to ambient and household fine-particulate matter (PM2.5) together are among the largest single causes of premature mortality in India according to the Global Burden of Disease Studies (GBD). Several recent investigations have estimated that household emissions are the largest contributor to ambient PM2.5 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.1900888116

    authors: Chowdhury S,Dey S,Guttikunda S,Pillarisetti A,Smith KR,Di Girolamo L

    更新日期:2019-05-28 00:00:00

  • Avian and mammalian receptors for 1,25-dihydroxyvitamin D3: in vitro translation to characterize size and hormone-dependent regulation.

    abstract::In vitro translation of cellular poly(A)+ RNA coupled with immunoprecipitation was developed as a technique for characterizing 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors and assessing receptor mRNA activity. Cell-free translation of poly(A)+ RNA isolated from chicken intestine revealed two immunoprecipitable fo...

    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.84.2.354

    authors: Mangelsdorf DJ,Pike JW,Haussler MR

    更新日期:1987-01-01 00:00:00

  • Crystal structure of the GlnZ-DraG complex reveals a different form of PII-target interaction.

    abstract::Nitrogen metabolism in bacteria and archaea is regulated by a ubiquitous class of proteins belonging to the P(II)family. P(II) proteins act as sensors of cellular nitrogen, carbon, and energy levels, and they control the activities of a wide range of target proteins by protein-protein interaction. The sensing mechanis...

    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.1108038108

    authors: Rajendran C,Gerhardt EC,Bjelic S,Gasperina A,Scarduelli M,Pedrosa FO,Chubatsu LS,Merrick M,Souza EM,Winkler FK,Huergo LF,Li XD

    更新日期:2011-11-22 00:00:00

  • In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation.

    abstract::Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) 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.1818871116

    authors: Davis MT,Hillmer A,Holmes SE,Pietrzak RH,DellaGioia N,Nabulsi N,Matuskey D,Angarita GA,Carson RE,Krystal JH,Esterlis I

    更新日期:2019-06-04 00:00:00

  • Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs.

    abstract::Evidence of endoplasmic reticulum (ER) stress has been found in lungs of patients with familial and sporadic idiopathic pulmonary fibrosis. We tested whether ER stress causes or exacerbates lung fibrosis by (i) conditional expression of a mutant form of surfactant protein C (L188Q SFTPC) found in familial interstitial...

    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.1107559108

    authors: Lawson WE,Cheng DS,Degryse AL,Tanjore H,Polosukhin VV,Xu XC,Newcomb DC,Jones BR,Roldan J,Lane KB,Morrisey EE,Beers MF,Yull FE,Blackwell TS

    更新日期:2011-06-28 00:00:00

  • Evolutionary alteration of ALOX15 specificity optimizes the biosynthesis of antiinflammatory and proresolving lipoxins.

    abstract::ALOX15 (12/15-lipoxygenase) orthologs have been implicated in maturational degradation of intracellular organelles and in the biosynthesis of antiinflammatory and proresolving eicosanoids. Here we hypothesized that lower mammals (mice, rats, pigs) express 12-lipoxygenating ALOX15 orthologs. In contrast, 15-lipoxygenat...

    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.1604029113

    authors: Adel S,Karst F,González-Lafont À,Pekárová M,Saura P,Masgrau L,Lluch JM,Stehling S,Horn T,Kuhn H,Heydeck D

    更新日期:2016-07-26 00:00:00

  • Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants.

    abstract::Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MMPs). Analysis of conditioned media by zymography revealed latent and active forms of collagenase (MMP-1, EC 3.4.24.7), 72-kDa gelatinase A (MMP-2, EC 3.4.24.24), and 92-kDa gelatinase B (MMP-9, EC 3.4.24.35). These protein...

    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.89.24.11789

    authors: Marbaix E,Donnez J,Courtoy PJ,Eeckhout Y

    更新日期:1992-12-15 00:00:00

  • Antigenic drift in type A influenza virus: peptide mapping and antigenic analysis of A/PR/8/34 (HON1) variants selected with monoclonal antibodies.

    abstract::Variants of A/PR/8/34 (HON1) influenza virus, having hemagglutinin molecules with probably a single altered antigenic determinant, were isolated by growing the virus in the presence of the monoclonal hybridoma antibody PEG-1. The variants were analyzed by peptide mapping and characterized antigenically by using PEG-1 ...

    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.76.3.1425

    authors: Laver WG,Gerhard W,Webster RG,Frankel ME,Air GM

    更新日期:1979-03-01 00:00:00

  • ACSS2-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection.

    abstract::Recent studies have shown that human cytomegalovirus (HCMV) can induce a robust increase in lipid synthesis which is critical for the success of infection. In mammalian cells the central precursor for lipid biosynthesis, cytosolic acetyl CoA (Ac-CoA), is produced by ATP-citrate lyase (ACLY) from mitochondria-derived c...

    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.1614268114

    authors: Vysochan A,Sengupta A,Weljie AM,Alwine JC,Yu Y

    更新日期:2017-02-21 00:00:00

  • Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer.

    abstract::Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in 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.1013224108

    authors: Sproul D,Nestor C,Culley J,Dickson JH,Dixon JM,Harrison DJ,Meehan RR,Sims AH,Ramsahoye BH

    更新日期:2011-03-15 00:00:00

  • Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway.

    abstract::Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV "jumps" from an infected animal to a person and is subsequently 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.0809698105

    authors: Strong JE,Wong G,Jones SE,Grolla A,Theriault S,Kobinger GP,Feldmann H

    更新日期:2008-11-18 00:00:00

  • Gene repression by the ferric uptake regulator in Pseudomonas aeruginosa: cycle selection of iron-regulated genes.

    abstract::The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). Novel targets of the Fur protein were isolated in a powerful SELEX (systematic evolution of ligands by exponential enrichment)-like cycle selection consisting of in vitro DNA-Fur ...

    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.93.9.4409

    authors: Ochsner UA,Vasil ML

    更新日期:1996-04-30 00:00:00

  • Site specific recA--independent recombination between bacterial plasmids: involvement of palindromes at the recombinational loci.

    abstract::A recA-independent recombinational event is described which results in insertion of an entire plasmid genome at a unique site of another plasmid, and coincident excision of a precisely defined DNA segment originally present at the point of the insertion. The resulting recombinant molecules subsequently can undergo sit...

    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.72.4.1373

    authors: Kopecko DJ,Cohen SN

    更新日期:1975-04-01 00:00:00

  • The B1-subunit of the H(+) ATPase is required for maximal urinary acidification.

    abstract::The multisubunit vacuolar-type H(+)ATPases mediate acidification of various intracellular organelles and in some tissues mediate H(+) secretion across the plasma membrane. Mutations in the B1-subunit of the apical H(+)ATPase that secretes protons in the distal nephron cause distal renal tubular acidosis in humans, a c...

    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.0506769102

    authors: Finberg KE,Wagner CA,Bailey MA,Paunescu TG,Breton S,Brown D,Giebisch G,Geibel JP,Lifton RP

    更新日期:2005-09-20 00:00:00

  • Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design.

    abstract::Inosine monophosphate dehydrogenase (IMPDH) controls a key metabolic step in the regulation of cell growth and differentiation. This step is the NAD-dependent oxidation of inosine 5' monophosphate (IMP) to xanthosine 5' monophosphate, the rate-limiting step in the synthesis of the guanine nucleotides. Two isoforms 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.96.7.3531

    authors: Colby TD,Vanderveen K,Strickler MD,Markham GD,Goldstein BM

    更新日期:1999-03-30 00:00:00

  • Ocean melting of the Zachariae Isstrøm and Nioghalvfjerdsfjorden glaciers, northeast Greenland.

    abstract::Zachariae Isstrøm (ZI) and Nioghalvfjerdsfjorden (79N) are marine-terminating glaciers in northeast Greenland that hold an ice volume equivalent to a 1.1-m global sea level rise. ZI lost its floating ice shelf, sped up, retreated at 650 m/y, and experienced a 5-gigaton/y mass loss. Glacier 79N has been more stable des...

    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.2015483118

    authors: An L,Rignot E,Wood M,Willis JK,Mouginot J,Khan SA

    更新日期:2021-01-12 00:00:00

  • Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila.

    abstract::Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytok...

    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.1516122113

    authors: Lamiable O,Kellenberger C,Kemp C,Troxler L,Pelte N,Boutros M,Marques JT,Daeffler L,Hoffmann JA,Roussel A,Imler JL

    更新日期:2016-01-19 00:00:00

  • Mechanism of ubiquitin transfer promoted by TRAF6.

    abstract::Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) plays a vital role in immune signal transduction pathways by acting as a ubiquitin ligase (E3) for Lys63-linked polyubiquitin chain synthesis. However, the detailed mechanism by which the TRAF6 RING dimer promotes ubiquitin transfer was unknown. Through ...

    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.1721788115

    authors: Fu TM,Shen C,Li Q,Zhang P,Wu H

    更新日期:2018-02-20 00:00:00