Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration.

Abstract:

:Spinocerebellar ataxia type 7 (SCA7) is characterized by cone-rod dystrophy retinal degeneration and is caused by a polyglutamine [poly(Q)] expansion within ataxin-7, a protein of previously unknown function. Here, we report that ataxin-7 is an integral component of the mammalian STAGA (SPT3-TAF9-ADA-GCN5 acetyltransferase) transcription coactivator complex, interacts directly with the GCN5 histone acetyltransferase component of STAGA, and mediates a direct interaction of STAGA with the CRX (cone-rod homeobox) transactivator of photoreceptor genes. Consistent with these results, chromatin immunoprecipitation assays document retinal-specific association of CRX, GCN5, and acetylated histone H3 with CRX target genes. RNA interference studies also implicate ataxin-7 and GCN5 in CRX-dependent gene activation, and histone deacetylase inhibitors restore the compromised expression of a CRX target gene in an ataxin-7-deficient background. Significantly, in relation to SCA7, poly(Q)-expanded ataxin-7 gets incorporated into STAGA and, in a dominant-negative manner, inhibits the nucleosomal histone acetylation function of STAGA GCN5 both in vitro and, based on chromatin immunoprecipitation assays, in SCA7 transgenic mice. These results suggest that the normal function of a poly(Q) disease protein may intersect with its pathogenic mechanism, an observation with significant implications for the molecular basis of all poly(Q) disorders and ultimately for their treatment.

authors

Palhan VB,Chen S,Peng GH,Tjernberg A,Gamper AM,Fan Y,Chait BT,La Spada AR,Roeder RG

doi

10.1073/pnas.0503505102

keywords:

subject

Has Abstract

pub_date

2005-06-14 00:00:00

pages

8472-7

issue

24

eissn

0027-8424

issn

1091-6490

pii

0503505102

journal_volume

102

pub_type

杂志文章
  • Transcription initiation in the histidine operon of Salmonella typhimurium.

    abstract::Evidence is presented for two natural transcription initiators positioned internally in the histidine operon of Salmonella typhimurium. They were detected using highly polar S. typhimurium his mutants as recipients for F' Escherichia coli his episomes. These intergeneric complementation tests provide a sensitive metho...

    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.65.4.925

    authors: Atkins JF,Loper JC

    更新日期:1970-04-01 00:00:00

  • Design of a retroviral-mediated ecdysone-inducible system and its application to the expression profiling of the PTEN tumor suppressor.

    abstract::We have engineered the ecdysone-inducible mammalian expression system for general retroviral delivery to cultured mammalian cells. We inducibly expressed PTEN in the glioblastoma cell line, U87MG, lacking this gene. Because nearly all cells are recruited on induction, we find both up- and down-regulated genes by cDNA ...

    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.221450598

    authors: Stolarov J,Chang K,Reiner A,Rodgers L,Hannon GJ,Wigler MH,Mittal V

    更新日期:2001-11-06 00:00:00

  • Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation.

    abstract::Myocardin and the myocardin-related transcription factors (MRTFs) A and B act as coactivators for serum response factor, which plays a key role in cardiovascular development. To determine the functions of MRTF-B in vivo, we generated MRTF-B mutant mice by targeted inactivation of the MRTF-B gene. We show that mice hom...

    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.0507346102

    authors: Oh J,Richardson JA,Olson EN

    更新日期:2005-10-18 00:00:00

  • Rlip depletion prevents spontaneous neoplasia in TP53 null mice.

    abstract::TP53 (p53) is a tumor suppressor whose functions are lost or altered in most malignancies. p53 homozygous knockout (p53-/-) mice uniformly die of spontaneous malignancy, typically T-cell lymphoma. RALBP1 (RLIP76, Rlip) is a stress-protective, mercapturic acid pathway transporter protein that also functions as a Ral ef...

    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.1719586115

    authors: Awasthi S,Tompkins J,Singhal J,Riggs AD,Yadav S,Wu X,Singh S,Warden C,Liu Z,Wang J,Slavin TP,Weitzel JN,Yuan YC,Awasthi M,Srivastava SK,Awasthi YC,Singhal SS

    更新日期:2018-04-10 00:00:00

  • Chelation of intracellular calcium blocks insulin action in the adipocyte.

    abstract::The hypothesis that intracellular Ca2+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca2+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulat...

    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.84.4.1025

    authors: Pershadsingh HA,Shade DL,Delfert DM,McDonald JM

    更新日期:1987-02-01 00:00:00

  • Sog/Chordin is required for ventral-to-dorsal Dpp/BMP transport and head formation in a short germ insect.

    abstract::Bone morphogenetic protein (BMP) signaling plays a major role in dorsoventral patterning in vertebrates and in Drosophila. Remarkably, in Tribolium, a beetle with an ancestral type of insect development, early BMP/dpp exhibits differential expression along the anteroposterior axis. However, the BMP/Dpp inhibitor Sog/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.0605154103

    authors: van der Zee M,Stockhammer O,von Levetzow C,Nunes da Fonseca R,Roth S

    更新日期:2006-10-31 00:00:00

  • CTIP2 is a negative regulator of P-TEFb.

    abstract::The positive transcription elongation factor b (P-TEFb) is involved in physiological and pathological events including inflammation, cancer, AIDS, and cardiac hypertrophy. The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcriptional repressor 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.1220136110

    authors: Cherrier T,Le Douce V,Eilebrecht S,Riclet R,Marban C,Dequiedt F,Goumon Y,Paillart JC,Mericskay M,Parlakian A,Bausero P,Abbas W,Herbein G,Kurdistani SK,Grana X,Van Driessche B,Schwartz C,Candolfi E,Benecke AG,Van Lin

    更新日期:2013-07-30 00:00:00

  • Spectrum of hot methane in astronomical objects using a comprehensive computed line list.

    abstract::Hot methane spectra are important in environments ranging from flames to the atmospheres of cool stars and exoplanets. A new spectroscopic line list, 10to10, for (12)CH4 containing almost 10 billion transitions is presented. This comprehensive line list covers a broad spectroscopic range and is applicable for temperat...

    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.1324219111

    authors: Yurchenko SN,Tennyson J,Bailey J,Hollis MD,Tinetti G

    更新日期:2014-07-01 00:00:00

  • Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme.

    abstract::Two functional human dUTP pyrophosphatase (dUTPase; EC 3.6.1.23) cDNAs were isolated from a cDNA expression library by genetic complementation in Escherichia coli. These cDNAs differed in size but exhibited a common overlapping DNA sequence. Contained within this sequence was a single long open reading frame sufficien...

    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.89.17.8020

    authors: McIntosh EM,Ager DD,Gadsden MH,Haynes RH

    更新日期:1992-09-01 00:00:00

  • Molecular and structural architecture of polyQ aggregates in yeast.

    abstract::Huntington's disease is caused by the expansion of a polyglutamine (polyQ) tract in the N-terminal exon of huntingtin (HttEx1), but the cellular mechanisms leading to neurodegeneration remain poorly understood. Here we present in situ structural studies by cryo-electron tomography of an established yeast model system ...

    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.1717978115

    authors: Gruber A,Hornburg D,Antonin M,Krahmer N,Collado J,Schaffer M,Zubaite G,Lüchtenborg C,Sachsenheimer T,Brügger B,Mann M,Baumeister W,Hartl FU,Hipp MS,Fernández-Busnadiego R

    更新日期:2018-04-10 00:00:00

  • Observing the 1H NMR signal of the myoglobin Val-E11 in myocardium: an index of cellular oxygenation.

    abstract::The 1H NMR signal from oxymyoglobin, a low-concentration diamagnetic protein, is visible in myocardial tissue. The methyl group of the Val-E11 resonates in a clear spectral region at -2.76 ppm and responds to dynamic changes in cellular oxygenation. With CO, the signal shifts to -2.4 ppm. The Val-E11 peak assignment 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.89.10.4731

    authors: Kreutzer U,Wang DS,Jue T

    更新日期:1992-05-15 00:00:00

  • Magnetic properties of oxyhemoglobin.

    abstract::When the magnetic susceptibility of frozen aqueous solutions of human oxyhemoglobin was measured in the range between 25 and 250 K, it showed a temperature-dependent behavior typical of a thermal equilibrium between a ground singlet state and an excited triplet state for two electrons per heme, the energy separation b...

    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.74.2.398

    authors: Cerdonio M,Congiu-Castellano A,Mogno F,Pispisa B,Romani GL,Vitale S

    更新日期:1977-02-01 00:00:00

  • DnaJ, DnaK, and GrpE heat shock proteins are required in oriP1 DNA replication solely at the RepA monomerization step.

    abstract::We have found that three Escherichia coli heat shock proteins, DnaK (the hsp70 homolog), DnaJ, and GrpE, function in oriP1 DNA replication in vitro solely to activate DNA binding by the replication initiator protein RepA. Activation results from the conversion of P1 or P7 RepA dimers to monomers that bind with high af...

    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.89.21.10345

    authors: Wickner S,Skowyra D,Hoskins J,McKenney K

    更新日期:1992-11-01 00:00:00

  • Species-specific metastasis of human tumor cells in the severe combined immunodeficiency mouse engrafted with human tissue.

    abstract::We have attempted to model human metastatic disease by implanting human target organs into the immunodeficient C.B-17 scid/scid (severe combined immunodeficiency; SCID) mouse, creating SCID-hu mice. Preferential metastasis to implants of human fetal lung and human fetal bone marrow occurred after i.v. injection of hum...

    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.92.10.4661

    authors: Shtivelman E,Namikawa R

    更新日期:1995-05-09 00:00:00

  • Semaphorin 3A growth cone collapse requires a sequence homologous to tarantula hanatoxin.

    abstract::Axonal guidance is key to the formation of neuronal circuitry. Semaphorin 3A (Sema 3A; previously known as semaphorin III, semaphorin D, and collapsin-1), a secreted subtype of the semaphorin family, is an important axonal guidance molecule in vitro and in vivo. The molecular mechanisms of the repellent activity of se...

    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.96.23.13501

    authors: Behar O,Mizuno K,Badminton M,Woolf CJ

    更新日期:1999-11-09 00:00:00

  • Role of two of the influenza virus core P proteins in recognizing cap 1 structures (m7GpppNm) on RNAs and in initiating viral RNA transcription.

    abstract::Purified influenza viral cores catalyze the entire process of viral RNA transcription, which includes the endonucleolytic cleavage of heterologous RNAs containing cap 1 (m(7)GpppNm) structures to generate capped primers 10-13 nucleotides long, the initiation of transcription via the incorporation of a guanosine residu...

    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.78.12.7355

    authors: Ulmanen I,Broni BA,Krug RM

    更新日期:1981-12-01 00:00:00

  • Lysinuric protein intolerance mutation is expressed in the plasma membrane of cultured skin fibroblasts.

    abstract::Lysinuric protein intolerance (LPI) is an autosomal recessive phenotype consistent with impaired transport of cationic amino acids at the basolateral membrane of intestinal and renal epithelia. On the assumption that the basolateral membrane of epithelial cells and plasma membrane of parenchymal cells are functional 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.84.21.7711

    authors: Smith DW,Scriver CR,Tenenhouse HS,Simell O

    更新日期:1987-11-01 00:00:00

  • Protein damage and death by radiation in Escherichia coli and Deinococcus radiodurans.

    abstract::Deinococcus radiodurans is among a small number of bacterial species that are extremely resistant to ionizing radiation, UV light, toxic chemicals, and desiccation. We measured proteome oxidation (i.e., protein carbonylation, PC) in D. radiodurans as well as in standard and evolved resistant strains of Escherichia col...

    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.1009312107

    authors: Krisko A,Radman M

    更新日期:2010-08-10 00:00:00

  • Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury.

    abstract::Semaphorin 4D (sema4D; CD100) is an integral membrane protein and the ligand for two receptors, CD72 and plexin-B1. Soluble sema4D has been shown to evoke angiogenic responses from endothelial cells and impair monocyte migration, but the origin of soluble sema4D, particularly at sites of vascular injury, has been uncl...

    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.0606344104

    authors: Zhu L,Bergmeier W,Wu J,Jiang H,Stalker TJ,Cieslak M,Fan R,Boumsell L,Kumanogoh A,Kikutani H,Tamagnone L,Wagner DD,Milla ME,Brass LF

    更新日期:2007-01-30 00:00:00

  • SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes.

    abstract::Neutrophils are immune cells that bind to, engulf, and destroy bacterial and fungal pathogens in infected tissue, and their clearance by apoptosis is essential for the resolution of inflammation. Killing involves both oxidative and nonoxidative processes, the oxidative pathway requiring electrogenic production of supe...

    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.0607914103

    authors: Fay AJ,Qian X,Jan YN,Jan LY

    更新日期:2006-11-14 00:00:00

  • Ancient DNA reveals the Arctic origin of Viking Age cod from Haithabu, Germany.

    abstract::Knowledge of the range and chronology of historic trade and long-distance transport of natural resources is essential for determining the impacts of past human activities on marine environments. However, the specific biological sources of imported fauna are often difficult to identify, in particular if species have a ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1710186114

    authors: Star B,Boessenkool S,Gondek AT,Nikulina EA,Hufthammer AK,Pampoulie C,Knutsen H,André C,Nistelberger HM,Dierking J,Petereit C,Heinrich D,Jakobsen KS,Stenseth NC,Jentoft S,Barrett JH

    更新日期:2017-08-22 00:00:00

  • Unbiased RNA-protein interaction screen by quantitative proteomics.

    abstract::Mass spectrometry (MS)-based quantitative interaction proteomics has successfully elucidated specific protein-protein, DNA-protein, and small molecule-protein interactions. Here, we developed a gel-free, sensitive, and scalable technology that addresses the important area of RNA-protein interactions. Using aptamer-tag...

    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.0812099106

    authors: Butter F,Scheibe M,Mörl M,Mann M

    更新日期:2009-06-30 00:00:00

  • A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.

    abstract::A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs inclu...

    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.90.10.4374

    authors: Levi M,Sällberg M,Rudén U,Herlyn D,Maruyama H,Wigzell H,Marks J,Wahren B

    更新日期:1993-05-15 00:00:00

  • Structure and function of bacterial ribosomes. XI. Dependence of 50S ribosomal assembly on simultaneous assembly of 30S subunits.

    abstract::Some spectinomycin-resistant mutants of Escherichia coli are cold-sensitive. They are unable to assemble both 30S and 50S ribosomal subunits at low temperatures. They accumulate two kinds of incomplete particles, related to 30S and 50S subunits respectively. A single mutation, causing an alteration in a 30S ribosomal ...

    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.67.3.1440

    authors: Nashimoto H,Nomura M

    更新日期:1970-11-01 00:00:00

  • Fusigenic viral liposome for gene therapy in cardiovascular diseases.

    abstract::To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) are complexed with liposomes that encapsulate oligodeoxynucleot...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 评论,杂志文章,评审

    doi:10.1073/pnas.93.21.11421

    authors: Dzau VJ,Mann MJ,Morishita R,Kaneda Y

    更新日期:1996-10-15 00:00:00

  • Genetic analysis of traditional and evolved Basmati and non-Basmati rice varieties by using fluorescence-based ISSR-PCR and SSR markers.

    abstract::The objective of the present study was to make use of efficient molecular marker systems to reveal genetic relationships in traditional and evolved Basmati (EB) and semidwarf non-Basmati (NB) rice varieties. A subset of three rice groups was analyzed by using 19 simple sequence repeat (SSR) loci and 12 inter-SSR-PCR p...

    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.042099099

    authors: Nagaraju J,Kathirvel M,Kumar RR,Siddiq EA,Hasnain SE

    更新日期:2002-04-30 00:00:00

  • Overview of the most prevalent hypothalamus-specific mRNAs, as identified by directional tag PCR subtraction.

    abstract::We applied the directional tag PCR subtractive hybridization method to construct a rat hypothalamic cDNA library from which cerebellar and hippocampal sequences had been depleted, enriching 20-30-fold for sequences expressed selectively in the hypothalamus. We studied a sample of 94 clones selected for enrichment in 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.93.16.8733

    authors: Gautvik KM,de Lecea L,Gautvik VT,Danielson PE,Tranque P,Dopazo A,Bloom FE,Sutcliffe JG

    更新日期:1996-08-06 00:00:00

  • New mechanistic studies on the proline-catalyzed aldol reaction.

    abstract::The mechanism of the proline-catalyzed aldol reaction has stimulated considerable debate, and despite limited experimental data, at least five different mechanisms have been proposed. Complementary to recent theoretical studies we have initiated an experimental program with the goal of clarifying some of the basic mec...

    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.0307979101

    authors: List B,Hoang L,Martin HJ

    更新日期:2004-04-20 00:00:00

  • Animal cells dependent on exogenous phosphatidylcholine for membrane biogenesis.

    abstract::A Chinese hamster ovary cell (CHO) mutant (strain 58), defective in CDP-choline synthetase (cholinephosphate cytidylyltransferase; CTP:cholinephosphate cytidylyltransferase, EC 2.7.7.15), is temperature sensitive for growth and contains less than half of the normal amount of phosphatidylcholine under nonpermissive con...

    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.79.6.1698

    authors: Esko JD,Nishijima M,Raetz CR

    更新日期:1982-03-01 00:00:00

  • Primary photochemistry of iron-depleted and zinc-reconstituted reaction centers from Rhodopseudomonas sphaeroides.

    abstract::The primary photochemistry of Fe-depleted and Zn-reconstituted reaction centers from Rhodopseudomonas sphaeroides R-26.1 was studied by transient absorption spectroscopy and compared with native, Fe(2+)-containing reaction centers. Excitation of metal-free reaction centers with 30-ps flashes produced the initial charg...

    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.83.17.6407

    authors: Kirmaier C,Holten D,Debus RJ,Feher G,Okamura MY

    更新日期:1986-09-01 00:00:00