Regulation of the proapoptotic factor Bax by Ku70-dependent deubiquitylation.

Abstract:

:The DNA end-joining protein Ku70 is one of several proteins that inhibit apoptosis by sequestering the proapoptotic factor Bax from the mitochondria. However, the molecular mechanism underlying Ku70-dependent inhibition of Bax is not fully understood. Here, we show that the absence of Ku70 results in the accumulation of ubiquitylated Bax. Under normal growth conditions, Bax ubiquitylation promotes its degradation. Upon induction of apoptosis in wild-type cells, a significant reduction in the levels of ubiquitylated Bax was observed, whereas in Ku70(-/-) cells, the ubiquitylated Bax was robustly accumulated. Addition of recombinant Ku70 into a protein extract of Ku70(-/-) cells resulted in a decrease in the levels of ubiquitylated Bax, even in the presence of proteasome inhibitors. Moreover, an in vitro deubiquitylation assay demonstrated that recombinant Ku70 hydrolyzed polyubiquitin chains into monoubiquitin units. Thus, Ku70 regulates apoptosis by sequestering Bax from the mitochondria and mediating Bax deubiquitylation. These results shed light on the role of proteasome inhibitors as tumor suppressors.

authors

Amsel AD,Rathaus M,Kronman N,Cohen HY

doi

10.1073/pnas.0706700105

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

5117-22

issue

13

eissn

0027-8424

issn

1091-6490

pii

0706700105

journal_volume

105

pub_type

杂志文章
  • Discovery of fossil lamprey larva from the Lower Cretaceous reveals its three-phased life cycle.

    abstract::Lampreys are one of the two surviving jawless vertebrate groups and one of a few vertebrate groups with the best exemplified metamorphosis during their life cycle, which consists of a long-lasting larval stage, a peculiar metamorphosis, and a relatively short adulthood with a markedly different anatomy. Although the f...

    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.1415716111

    authors: Chang MM,Wu F,Miao D,Zhang J

    更新日期:2014-10-28 00:00:00

  • Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo.

    abstract::The perforant path (PP) undergoes synaptic changes in the course of aging and dementia. Previous studies attempting to assess the integrity of the PP in humans using diffusion tensor imaging (DTI) were limited by low resolution and the inability to identify PP fibers specifically. Here we present an application of DTI...

    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.1002113107

    authors: Yassa MA,Muftuler LT,Stark CE

    更新日期:2010-07-13 00:00:00

  • Tumorigenic methylcholanthrene transformants of C3H/10T1/2 cells have a common nucleotide alteration in the c-Ki-ras gene.

    abstract::The polymerase chain reaction was used to amplify DNA surrounding the codon 12 region of the c-Ki-ras gene from C3H/10T1/2 cells and from a number of 3-methylcholanthrene (MCA)-transformed derivatives of these cells. Sequence analysis demonstrated that tumorigenic MCAC116/39 cells, known by DNA-mediated transfection 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.86.5.1608

    authors: Chen AC,Herschman HR

    更新日期:1989-03-01 00:00:00

  • Ultradonut topology of the nuclear envelope.

    abstract::The nuclear envelope is a unique topological structure formed by lipid membranes in eukaryotic cells. Unlike other membrane structures, the nuclear envelope comprises two concentric membrane shells fused at numerous sites with toroid-shaped pores that impart a "geometric" genus on the order of thousands. Despite the i...

    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.1604777113

    authors: Torbati M,Lele TP,Agrawal A

    更新日期:2016-10-04 00:00:00

  • Regulatory interactions of calmodulin-binding proteins: phosphorylation of calcineurin by autophosphorylated Ca2+/calmodulin-dependent protein kinase II.

    abstract::The Ca2+/calmodulin (CaM)-dependent protein phosphatase calcineurin is rapidly phosphorylated (0.8 mol of 32PO4 per mol of 60-kDa subunit of calcineurin) by brain Ca2+/CaM-dependent protein kinase II (CaM-kinase II). This reaction requires the autophosphorylated, Ca2+-independent form of CaM-kinase II since Ca2+/CaM 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.85.18.7001

    authors: Hashimoto Y,King MM,Soderling TR

    更新日期:1988-09-01 00:00:00

  • Metallacycle-cored supramolecular assemblies with tunable fluorescence including white-light emission.

    abstract::Control over the fluorescence of supramolecular assemblies is crucial for the development of chemosensors and light-emitting materials. Consequently, the postsynthetic modification of supramolecular structures via host-guest interactions has emerged as an efficient strategy in recent years that allows the facile tunin...

    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.1702510114

    authors: Zhang M,Yin S,Zhang J,Zhou Z,Saha ML,Lu C,Stang PJ

    更新日期:2017-03-21 00:00:00

  • Catalysis and rotation of F1 motor: cleavage of ATP at the catalytic site occurs in 1 ms before 40 degree substep rotation.

    abstract::F1, a water-soluble portion of FoF1-ATP synthase, is an ATP hydrolysis-driven rotary motor. The central gamma-subunit rotates in the alpha 3 beta 3 cylinder by repeating the following four stages of rotation: ATP-binding dwell, rapid 80 degrees substep rotation, interim dwell, and rapid 40 degrees substep rotation. At...

    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.2434983100

    authors: Shimabukuro K,Yasuda R,Muneyuki E,Hara KY,Kinosita K Jr,Yoshida M

    更新日期:2003-12-09 00:00:00

  • Cadmium and iron transport by members of a plant metal transporter family in Arabidopsis with homology to Nramp genes.

    abstract::Metal cation homeostasis is essential for plant nutrition and resistance to toxic heavy metals. Many plant metal transporters remain to be identified at the molecular level. In the present study, we have isolated AtNramp cDNAs from Arabidopsis and show that these genes complement the phenotype of a metal uptake defici...

    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.97.9.4991

    authors: Thomine S,Wang R,Ward JM,Crawford NM,Schroeder JI

    更新日期:2000-04-25 00:00:00

  • Quantifying signaling-induced reorientation of T cell receptors during immunological synapse formation.

    abstract::Productive T cell recognition of antigen-presenting cells (APCs) is normally accompanied by the formation of a cell-cell contact called the "immunological synapse." Our understanding of the steps leading up to this formation has been limited by the absence of tools for analyzing 3D surfaces and surface distributions 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.192573999

    authors: Moss WC,Irvine DJ,Davis MM,Krummel MF

    更新日期:2002-11-12 00:00:00

  • Message passing on networks with loops.

    abstract::Message passing is a fundamental technique for performing calculations on networks and graphs with applications in physics, computer science, statistics, and machine learning, including Bayesian inference, spin models, satisfiability, graph partitioning, network epidemiology, and the calculation of matrix eigenvalues....

    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.1914893116

    authors: Cantwell GT,Newman MEJ

    更新日期:2019-11-19 00:00:00

  • Thermodynamic aspects of the linkage between binding of chloride and oxygen to human hemoglobin.

    abstract::Oxygen isotherms of human hemoglobin measured in distilled water and in solutions of sodium chloride in the concentration range from 0.02 to 3.0 M indicate that the oxygen affinity decreases up to about 1 M salt and then begins to increase. The isotherms obtained in the range from 0.02 to 0.6 M sodium chloride, at 37 ...

    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.74.10.4135

    authors: Haire RN,Hedlund BE

    更新日期:1977-10-01 00:00:00

  • Genetic predisposition of transgenic mouse melanocytes to melanoma results in malignant melanoma after exposure to a low ultraviolet B intensity nontumorigenic for normal melanocytes.

    abstract::Tyr-SV40E transgenic mice are susceptible to melanoma due to simian virus 40 oncogenic sequences specifically expressed in pigment cells. Skin melanomas form relatively late. Therefore, melanocyte cell lines have been established from very young transgenic animals, when they showed no skin lesions, so that the spontan...

    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.89.20.9534

    authors: Larue L,Dougherty N,Mintz B

    更新日期:1992-10-15 00:00:00

  • mRNA for surface immunoglobulin gamma chains encodes a highly conserved transmembrane sequence and a 28-residue intracellular domain.

    abstract::To probe the structure of the gamma heavy chain of membrane IgG and the mRNA and gene segments that encode it, we have analyzed cDNA clones derived from a gamma 1 membrane RNA of B lymphoma 2PK-3. The nucleotide sequence of the clones indicated that membrane gamma 1 chains bear a COOH-terminal 71-residue segment that ...

    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.79.6.2008

    authors: Tyler BM,Cowman AF,Gerondakis SD,Adams JM,Bernard O

    更新日期:1982-03-01 00:00:00

  • Activation and repolarization of the normal human heart under complete physiological conditions.

    abstract::Knowledge of normal human cardiac excitation stems from isolated heart or intraoperative mapping studies under nonphysiological conditions. Here, we use a noninvasive imaging modality (electrocardiographic imaging) to study normal activation and repolarization in intact unanesthetized healthy adults under complete phy...

    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.0601533103

    authors: Ramanathan C,Jia P,Ghanem R,Ryu K,Rudy Y

    更新日期:2006-04-18 00:00:00

  • Esterase 6 in Drosophila melanogaster: reproductive function of active and null males at low temperature.

    abstract::Esterase 6 is a polymorphic carboxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1) localized to the reproductive tract of male Drosophila melanogaster and transferred to females at copulation. The reproductive fitness of males is strongly affected by temperature and the esterase 6 alleles (active versus null) that ...

    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.79.9.2962

    authors: Gilbert DG,Richmond RC

    更新日期:1982-05-01 00:00:00

  • Distinct coated vesicles labeled for p200 bud from trans-Golgi network membranes.

    abstract::Golgi-associated cytoplasmic proteins, such as the coatomer protein complex, are required for vesicle budding and trafficking. We have previously described a cytoplasmic phosphoprotein, p200, which binds dynamically and specifically to Golgi membranes. The p200 protein is dissociated from Golgi membranes in the presen...

    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.92.7.2874

    authors: Narula N,Stow JL

    更新日期:1995-03-28 00:00:00

  • A general genetic approach in Escherichia coli for determining the mechanism(s) of action of tumoricidal agents: application to DMP 840, a tumoricidal agent.

    abstract::We describe here a simple and easily manipulatable Escherichia coli-based genetic system that permits us to identify bacterial gene products that modulate the sensitivity of bacteria to tumoricidal agents, such as DMP 840, a bisnaphthalimide drug. To the extent that the action of these agents is conserved, these studi...

    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.92.19.8950

    authors: Chatterjee PK,Sternberg NL

    更新日期:1995-09-12 00:00:00

  • Direct evidence for a predominantly exolytic processive mechanism for depolymerization of heparin-like glycosaminoglycans by heparinase I.

    abstract::Heparinase I from Flavobacterium heparinum has important uses for elucidating the complex sequence heterogeneity of heparin-like glycosaminoglycans (HLGAGs). Understanding the biological function of HLGAGs has been impaired by the limited methods for analysis of pure or mixed oligosaccharide fragments. Here, we use me...

    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.95.8.4182

    authors: Ernst S,Rhomberg AJ,Biemann K,Sasisekharan R

    更新日期:1998-04-14 00:00:00

  • Colloquium paper: phylogenetic trees and the future of mammalian biodiversity.

    abstract::Phylogenies describe the origins and history of species. However, they can also help to predict species' fates and so can be useful tools for managing the future of biodiversity. This article starts by sketching how phylogenetic, geographic, and trait information can be combined to elucidate present mammalian diversit...

    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.0801917105

    authors: Davies TJ,Fritz SA,Grenyer R,Orme CD,Bielby J,Bininda-Emonds OR,Cardillo M,Jones KE,Gittleman JL,Mace GM,Purvis A

    更新日期:2008-08-12 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

  • Aphidicolin inhibits the synthesis and joining of short DNA fragments but not the union of 10-kilobase DNA replication intermediates.

    abstract::DNA replication intermediates in human melanoma cells have been investigated by using the drug aphidicolin, which inhibits DNA polymerase alpha. In untreated cells, Okazaki fragments and 10-kilobase (kb) DNA intermediates are formed. In aphidicolin-treated cells, the replication fork is stopped and there is no formati...

    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.80.13.3996

    authors: Lönn U,Lönn S

    更新日期:1983-07-01 00:00:00

  • IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity.

    abstract::Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. H...

    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.1009152108

    authors: Ricardo-Gonzalez RR,Red Eagle A,Odegaard JI,Jouihan H,Morel CR,Heredia JE,Mukundan L,Wu D,Locksley RM,Chawla A

    更新日期:2010-12-28 00:00:00

  • Gangliosides are neuronal ligands for myelin-associated glycoprotein.

    abstract::Nerve cells depend on specific interactions with glial cells for proper function. Myelinating glial cells are thought to associate with neuronal axons, in part, via the cell-surface adhesion protein, myelin-associated glycoprotein (MAG). MAG is also thought to be a major inhibitor of neurite outgrowth (axon regenerati...

    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.93.2.814

    authors: Yang LJ,Zeller CB,Shaper NL,Kiso M,Hasegawa A,Shapiro RE,Schnaar RL

    更新日期:1996-01-23 00:00:00

  • The impact of the certainty context on the process of choice.

    abstract::In this study we examine how the introduction of a reference lottery with nonrandom outcomes alters the way in which choices among pairs of lotteries are made, even if it does not alter the choices. We use different domains (some of the lotteries produce gains, other losses) and different contexts (one member of the 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.0530279100

    authors: Dickhaut J,McCabe K,Nagode JC,Rustichini A,Smith K,Pardo JV

    更新日期:2003-03-18 00:00:00

  • Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation.

    abstract::The circadian clock in eukaryotes controls transcriptional and posttranscriptional events, including regulation of the levels and phosphorylation state of translation factors. However, the mechanisms underlying clock control of translation initiation, and the impact of this potential regulation on rhythmic protein syn...

    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.1918459117

    authors: Karki S,Castillo K,Ding Z,Kerr O,Lamb TM,Wu C,Sachs MS,Bell-Pedersen D

    更新日期:2020-05-19 00:00:00

  • Genomic clone for sandbar shark lambda light chain: generation of diversity in the absence of gene rearrangement.

    abstract::While the general structure of immunoglobulin chains has remained relatively unchanged throughout evolution, the organization of the genes encoding these molecules differs substantially. To understand how the rearranging immunoglobulin system arose, it is necessary to examine living representatives of the most early v...

    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.90.21.9882

    authors: Hohman VS,Schuchman DB,Schluter SF,Marchalonis JJ

    更新日期:1993-11-01 00:00:00

  • Large-scale comparison of intron positions in mammalian genes shows intron loss but no gain.

    abstract::We compared intron-exon structures in 1,560 human-mouse orthologs and 360 mouse-rat orthologs. The origin of differences in intron positions between species was inferred by comparison with an outgroup, Fugu for human-mouse and human for mouse-rat. Among 10,020 intron positions in the human-mouse comparison, we found u...

    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.1232297100

    authors: Roy SW,Fedorov A,Gilbert W

    更新日期:2003-06-10 00:00:00

  • Energetics of the exchangeable quinone, QB, in Photosystem II.

    abstract::Photosystem II (PSII), the light-driven water/plastoquinone photooxidoreductase, is of central importance in the planetary energy cycle. The product of the reaction, plastohydroquinone (PQH2), is released into the membrane from the QB site, where it is formed. A plastoquinone (PQ) from the membrane pool then binds int...

    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.1910675116

    authors: De Causmaecker S,Douglass JS,Fantuzzi A,Nitschke W,Rutherford AW

    更新日期:2019-09-24 00:00:00

  • Bacteriophage T4 polynucleotide kinase triggers degradation of mRNAs.

    abstract::The bacteriophage T4-encoded RegB endoribonuclease is produced during the early stage of phage development and targets mostly (but not exclusively) the Shine-Dalgarno sequences of early genes. In this work, we show that the degradation of RegB-cleaved mRNAs depends on a functional T4 polynucleotide kinase/phosphatase ...

    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.1119802109

    authors: Durand S,Richard G,Bontems F,Uzan M

    更新日期:2012-05-01 00:00:00

  • Valproic acid interactions with the NavMs voltage-gated sodium channel.

    abstract::Valproic acid (VPA) is an anticonvulsant drug that is also used to treat migraines and bipolar disorder. Its proposed biological targets include human voltage-gated sodium channels, among other membrane proteins. We used the prokaryotic NavMs sodium channel, which has been shown to be a good exemplar for drug binding ...

    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.1909696116

    authors: Zanatta G,Sula A,Miles AJ,Ng LCT,Torella R,Pryde DC,DeCaen PG,Wallace BA

    更新日期:2019-12-10 00:00:00