Rapid deubiquitination of nucleosomal histones in human tumor cells caused by proteasome inhibitors and stress response inducers: effects on replication, transcription, translation, and the cellular stress response.


:The proteasome inhibitors, lactacystin and N-acetyl-leucyl-leucyl-norlucinal, caused a rapid and near-complete loss of approximately 22-23-kDa ubiquitinated nucleoproteins, which we have identified as monoubiquitinated nucleosomal histones H2A and H2B by immunological and two-dimensional electrophoretic techniques. In human SKBr3 breast tumor cells, depletion of monoubiquitinated histones by the proteasome inhibitors coincided with the accumulation of high molecular weight ubiquitinated proteins in both nucleoprotein and cytosolic fractions and decreased unconjugated ubiquitin in the cytosol, without changes in the nonubiquitinated core histones. Unconjugated ubiquitin was not detected in isolated tumor cell nuclei. A similar loss in monoubiquitinated histones occurred in cells harboring a defective, temperature-sensitive mutation of the ubiquitin-activating E1 enzyme, after these cells were elevated from 33 degrees C to the non-permissive temperature of 39 degrees C. DNA replication and RNA transcription were decreased by the proteasome inhibitors most strongly after 90% of the ubiquitin had been removed from ubiquitinated histones H2A and H2B, suggesting a relationship between the nucleosomal histone ubiquitin status and the processing of genetic information. Interestingly, although both proteasome inhibitors caused a generalized decrease in methionine incorporation into proteins, they strongly induced the synthesis of the hsp72 and hsp90 stress proteins. Finally, treating cells with heat-shock at 43 degrees C, with stress response-provoking chemicals or with several other proteasome inhibitors caused ubiquitinated proteins to accumulate, depleted free ubiquitin, and concomitantly decreased nucleosomal monoubiquitinated histones. These results suggest that deubiquitination of nucleosomal histones H2A and H2B may play a previously unrecognized role in the cellular stress response, as well as in the processing of chromatin, and emphasize the important role of the proteasome in cellular homeostasis.






Mimnaugh EG,Chen HY,Davie JR,Celis JE,Neckers L




Has Abstract


1997-11-25 00:00:00














  • Calorimetric studies of adenosine 5'-triphosphate hydrolysis by heavy meromyosin.

    abstract::The heat production for the reaction steps of ATP hydrolysis by heavy meromyosin has been reexamined by using a reaction-type calorimeter. So far, the values reported for the heat production have varied substantially among research groups. The present results obtained in 0.3 M KCl, 10 mM MgCl2, and 20 mM Tris-HCl at p...


    pub_type: 杂志文章


    authors: Yamada T,Shimizu H,Suga H

    更新日期:1981-07-21 00:00:00

  • 2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A.T --> C.G mutations caused by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate by suppressing its degradation upon replication in a HeLa extract.

    abstract::The coexistence effects of multiple kinds of oxidized deoxyribonucleotides were examined using an SV40 origin-dependent in vitro replication system with a HeLa extract. Oxidized dGTP and dATP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP) and 2-hydroxy-2'-deoxyadenosine 5'-triphosphate (2-OH-dATP), were used...


    pub_type: 杂志文章


    authors: Satou K,Kasai H,Masutani C,Hanaoka F,Harashima H,Kamiya H

    更新日期:2007-06-05 00:00:00

  • Properties of tRNA species modified in the 3'-terminal ribose moiety in an eukaryotic ribosomal system.

    abstract::Phe-tRNAPhe species modified on the 3'-terminal ribose residue were investigated for their ability to participate in individual steps of the elongation cycle using eukaryotic ribosomes from reticulocytes. None of the Phe-tRNAs used, namely Phe-tRNAPhe-C-C-3'dA, Phe-tRNAPhe-C-C-3'-NH2A, and Phe-tRNAPhe-C-C-Aoxi-red, ca...


    pub_type: 杂志文章


    authors: Baksht E,de Groot N,Sprinzl M,Cramer F

    更新日期:1976-08-10 00:00:00

  • Complex structures between the N-type calcium channel (CaV2.2) and ω-conotoxin GVIA predicted via molecular dynamics.

    abstract::The N-type voltage-gated Ca(2+) channel CaV2.2 is one of the important targets for pain management. ω-Conotoxins isolated from venoms of cone snails, which specifically inhibit CaV2.2, are promising scaffolds for novel analgesics. The inhibitory action of ω-conotoxins on CaV2.2 has been examined experimentally, but th...


    pub_type: 杂志文章


    authors: Chen R,Chung SH

    更新日期:2013-05-28 00:00:00

  • Kinetics and concentration dependency of cAMP-induced desensitization of a subpopulation of surface cAMP receptors in Dictyostelium discoideum.

    abstract::Extracellular cAMP induces the rapid activation of guanylate cyclase, which adapts within 10 s to constant cAMP concentrations. A new response can be induced either by a higher cAMP concentration or by the same cAMP concentration at some time (t1/2 = 90 s) after removal of the previous stimulus. Stimulation of guanyla...


    pub_type: 杂志文章


    authors: Van Haastert PJ

    更新日期:1987-11-17 00:00:00

  • Cholesterol efflux from macrophage foam cells is enhanced by active phospholipid transfer protein through generation of two types of acceptor particles.

    abstract::Phospholipid transfer protein (PLTP) is expressed by macrophage-derived foam cells in human atherosclerotic lesions, suggesting a regulatory role for PLTP in cellular cholesterol homeostasis. However, the exact role of PLTP in the reverse cholesterol transport pathway is not known. PLTP is present in plasma as two for...


    pub_type: 杂志文章


    authors: Vikstedt R,Metso J,Hakala J,Olkkonen VM,Ehnholm C,Jauhiainen M

    更新日期:2007-10-23 00:00:00

  • Tritium isotope effects in adenosylcobalamin-dependent methylmalonyl-CoA mutase.

    abstract::Methylmalonyl-CoA mutase from Propionibacterium shermanii is an adenosylcobalamin-dependent enzyme which catalyzes the reversible isomerization of methylmalonyl-CoA and succinyl-CoA. The rate of tritium loss from 5'-[3H]adenosylcobalamin during the enzymic reaction and the relative rates of tritium appearance in subst...


    pub_type: 杂志文章


    authors: Meier TW,Thomä NH,Leadlay PF

    更新日期:1996-09-10 00:00:00

  • Interaction of alpha-dansylated peptide inhibitors with porcine pepsin: detection of complex formation by fluorescence energy transfer and chromatography and evidence for a two-step binding scheme.

    abstract::Peptide inhibitors, specifically labeled at the alpha-amino terminus by dansylation, have been prepared by utilizing solid-phase peptide synthesis. Changes in fluorescence have been observed upon mixing these peptides with porcine pepsin that can be attributed to the formation of at least two complexes. Energy transfe...


    pub_type: 杂志文章


    authors: Dunn BM,Pham C,Raney L,Abayasekara D,Gillespie W,Hsu A

    更新日期:1981-12-08 00:00:00

  • Purification and functional characterization of phiX174 lysis protein E.

    abstract::Two classes of bacteriophages, the single-stranded DNA Microviridae and the single-stranded RNA Alloleviviridae, accomplish lysis by expressing "protein antibiotics", or polypeptides that inhibit cell wall biosynthesis. Previously, we have provided genetic and physiological evidence that E, a 91-amino acid membrane pr...


    pub_type: 杂志文章


    authors: Zheng Y,Struck DK,Young R

    更新日期:2009-06-09 00:00:00

  • L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity.

    abstract::Progressive cerebral amyloid beta-protein (A beta) deposition is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels of A beta(42) peptide formation have been linked to early-onset familial AD-causing gene mutations in the amyloid beta-protein precursor (A beta PP) and the ...


    pub_type: 杂志文章


    authors: Shearman MS,Beher D,Clarke EE,Lewis HD,Harrison T,Hunt P,Nadin A,Smith AL,Stevenson G,Castro JL

    更新日期:2000-08-01 00:00:00

  • Factor Va-factor Xa interaction. Effects of phospholipid vesicles of varying composition.

    abstract::The interaction between factor Xa and factor Va was investigated both in solution and in the presence of phospholipid vesicles with varying contents of phosphatidylserine. The binding parameters were inferred from the kinetics of prothrombin activation. Factor Xa and factor Va form in solution an equimolar complex wit...


    pub_type: 杂志文章


    authors: Lindhout T,Govers-Riemslag JW,van de Waart P,Hemker HC,Rosing J

    更新日期:1982-10-26 00:00:00

  • Characterization of lens alpha-crystallin tryptophan microenvironments by room temperature phosphorescence spectroscopy.

    abstract::Room temperature phosphorescence techniques were used to study the structural and dynamic features of the tryptophan residues in bovine alpha-crystallin. Upon excitation at 290 nm, the characteristic signature of tryptophan phosphorescence was observed with an emission maximum at 442 +/- 2 nm. The phosphorescence inte...


    pub_type: 杂志文章


    authors: Berger JW,Vanderkooi JM

    更新日期:1989-06-27 00:00:00

  • Structural basis for substrate binding and the catalytic mechanism of type III pantothenate kinase.

    abstract::Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exempli...


    pub_type: 杂志文章


    authors: Yang K,Strauss E,Huerta C,Zhang H

    更新日期:2008-02-05 00:00:00

  • Isolation and characterization of a new endo-beta-galactosidase from Diplococcus pneumoniae.

    abstract::An endo-beta-galactosidase, which hydrolyzes the internal beta-galactosidic linkages of R----GlcNAc (or GalNAc) beta 1----3Gal beta 1----4GlcNAc (or Glc), was isolated from the culture supernatant of Diplococcus pneumoniae. The enzyme, named endo-beta-galactosidase DII, hydrolyzed linear N-acetyllactosamine repeating ...


    pub_type: 杂志文章


    authors: Fukuda MN

    更新日期:1985-04-23 00:00:00

  • Solution structure of the DNA methyl phosphotriester repair domain of Escherichia coli Ada.

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    pub_type: 杂志文章


    authors: Myers LC,Verdine GL,Wagner G

    更新日期:1993-12-28 00:00:00

  • Triple helix forming TRIPside molecules that target mixed purine/pyrimidine DNA sequences.

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    pub_type: 杂志文章


    authors: Li JS,Shikiya R,Marky LA,Gold B

    更新日期:2004-02-17 00:00:00

  • Click chemistry and bioorthogonal reactions: unprecedented selectivity in the labeling of biological molecules.

    abstract::In recent years, a number of bioorthogonal reactions have been developed, exemplified by click chemistry, that enable the efficient formation of a specific product, even within a highly complex chemical environment. While the exquisite selectivity and reliability of these transformations have led to their broad applic...


    pub_type: 杂志文章,评审


    authors: Best MD

    更新日期:2009-07-21 00:00:00

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    pub_type: 杂志文章


    authors: Budiman ME,Bierbach U,Alexander RW

    更新日期:2005-08-23 00:00:00

  • Cryoenzymology of chymotrypsin: the detection of intermediates in the catalysis of a specific anilide substrate.

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    pub_type: 杂志文章


    authors: Fink AL

    更新日期:1976-04-06 00:00:00

  • The linker between SH2 and kinase domains positively regulates catalysis of the Tec family kinases.

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    pub_type: 杂志文章


    authors: Joseph RE,Min L,Andreotti AH

    更新日期:2007-05-08 00:00:00

  • Post-translational modifications of aquaporin 0 (AQP0) in the normal human lens: spatial and temporal occurrence.

    abstract::Because of the lack of protein turnover in fiber cells of the ocular lens, Aquaporin 0 (AQP0), the most abundant membrane protein in the lens, undergoes extensive post-translational modification with fiber cell age. To map the distribution of modified forms of AQP0 within the lens, normal human lenses ranging in age f...


    pub_type: 杂志文章


    authors: Ball LE,Garland DL,Crouch RK,Schey KL

    更新日期:2004-08-03 00:00:00

  • Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e.

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    pub_type: 杂志文章


    authors: Bjarnason JB,Tu AT

    更新日期:1978-08-08 00:00:00

  • On the mechanism of activation of the BLUF domain of AppA.

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    pub_type: 杂志文章


    authors: Laan W,Gauden M,Yeremenko S,van Grondelle R,Kennis JT,Hellingwerf KJ

    更新日期:2006-01-10 00:00:00

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    pub_type: 杂志文章


    authors: Andersen JF,Ding XD,Balfour C,Shokhireva TK,Champagne DE,Walker FA,Montfort WR

    更新日期:2000-08-22 00:00:00

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    pub_type: 杂志文章


    authors: Kinosian HJ,Selden LA,Gershman LC,Estes JE

    更新日期:2000-10-31 00:00:00

  • Thermodynamics of transient conformations in the folding pathway of barnase: reorganization of the folding intermediate at low pH.

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    pub_type: 杂志文章


    authors: Oliveberg M,Fersht AR

    更新日期:1996-02-27 00:00:00

  • Relationship of the oxidation state of the iron-sulfur cluster of aconitase to activity and substrate binding.

    abstract::It is known that aconitase from mammalian mitochondria is only partially active as isolated but may be activated by incubation with iron, ascorbate, and a thiol, or with dithionite. It has been suggested that the added Fe in the activation mixture is essential for activation and that it is incorporated in the enzyme [...


    pub_type: 杂志文章


    authors: Ramsay RR,Dreyer JL,Schloss JV,Jackson RH,Coles CJ,Beinert H,Cleland WW,Singer TP

    更新日期:1981-12-22 00:00:00

  • pH-Dependent conformational stability of the ribotoxin alpha-sarcin and four active site charge substitution variants.

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    pub_type: 杂志文章


    authors: García-Mayoral MF,del Pozo AM,Campos-Olivas R,Gavilanes JG,Santoro J,Rico M,Laurents DV,Bruix M

    更新日期:2006-11-21 00:00:00

  • Collagen biosynthesis by cultured Chinese hamster lung cells. Cell-free synthesis of procollagen alpha chains.

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    pub_type: 杂志文章


    authors: Haralson MA,Frey KL,Mitchell WM

    更新日期:1978-03-07 00:00:00

  • Modulator protein as a component of the myosin light chain kinase from chicken gizzard.

    abstract::The Ca2+-dependent regulation of smooth muscle actomyosin involves a myosin light chain kinase (ATP: myosin light chain phosphotransferase). It has been shown (Dabrowska, R., Aromatorio, D., Sherry, J.M.F., and Hartshorne, D.J. 1977, Biochem. Biophys. Res. Commun. 78, 1263) that the kinase is composed of two proteins ...


    pub_type: 杂志文章


    authors: Dabrowska R,Sherry JM,Aromatorio DK,Hartshorne DJ

    更新日期:1978-01-24 00:00:00