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.
journal_name
Proc Natl Acad Sci U S Aauthors
Landry J,Sutton A,Tafrov ST,Heller RC,Stebbins J,Pillus L,Sternglanz Rdoi
10.1073/pnas.110148297keywords:
subject
Has Abstractpub_date
2000-05-23 00:00:00pages
5807-11issue
11eissn
0027-8424issn
1091-6490pii
110148297journal_volume
97pub_type
杂志文章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
更新日期:1989-02-01 00:00:00
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
更新日期:1982-12-01 00:00:00
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
更新日期:2005-12-20 00:00:00
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
更新日期:2010-12-14 00:00:00
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
更新日期:2014-12-09 00:00:00
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
更新日期:1998-06-09 00:00:00
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
更新日期:1996-03-19 00:00:00
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
更新日期:1986-12-01 00:00:00
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
更新日期:1972-01-01 00:00:00
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
更新日期:2020-11-24 00:00:00
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
更新日期:1982-08-01 00:00:00
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
更新日期:2017-02-14 00:00:00
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
更新日期:2019-05-28 00:00:00
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
更新日期:1987-01-01 00:00:00
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
更新日期:2011-11-22 00:00:00
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
更新日期:2019-06-04 00:00:00
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
更新日期:2011-06-28 00:00:00
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
更新日期:2016-07-26 00:00:00
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
更新日期:1992-12-15 00:00:00
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
更新日期:1979-03-01 00:00:00
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
更新日期:2017-02-21 00:00:00
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
更新日期:2011-03-15 00:00:00
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
更新日期:2008-11-18 00:00:00
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
更新日期:1996-04-30 00:00:00
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
更新日期:1975-04-01 00:00:00
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
更新日期:2005-09-20 00:00:00
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
更新日期:1999-03-30 00:00:00
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
更新日期:2021-01-12 00:00:00
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
更新日期:2016-01-19 00:00:00
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
更新日期:2018-02-20 00:00:00