Cellular Defenses against Unfolded Proteins

THE UBIQUITIN SYSTEM

1998 • 8,360 citations

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

1997 • 7,814 citations

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism

1998 • 5,063 citations

HEAT-SHOCK PROTEINS, MOLECULAR CHAPERONES, AND THE STRESS RESPONSE: Evolutionary and Ecological Physiology

1999 • 4,041 citations

α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies

1998 • 2,898 citations

The Hsp70 and Hsp60 Chaperone Machines

1998 • 2,793 citations

Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain

1997 • 2,762 citations

Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules

1994 • 2,480 citations

STRUCTURE AND FUNCTIONS OF THE 20S AND 26S PROTEASOMES

1996 • 2,408 citations

Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation

1997 • 2,184 citations

Aggresomes: A Cellular Response to Misfolded Proteins

1998 • 2,116 citations

Dopaminergic Loss and Inclusion Body Formation in α-Synuclein Mice: Implications for Neurodegenerative Disorders

2000 • 1,729 citations

Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway

2000 • 1,703 citations

Huntingtin Acts in the Nucleus to Induce Apoptosis but Death Does Not Correlate with the Formation of Intranuclear Inclusions

1998 • 1,592 citations

Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.

1998 • 1,546 citations

Oxidative Damage Linked to Neurodegeneration by Selective α-Synuclein Nitration in Synucleinopathy Lesions

2000 • 1,526 citations

Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome

2000 • 1,484 citations

Rapid degradation of a large fraction of newly synthesized proteins by proteasomes

2000 • 1,477 citations

Heat shock proteins.

1990 • 1,365 citations

Hsp104, Hsp70, and Hsp40

1998 • 1,346 citations

Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene

1997 • 1,229 citations

Repression of Heat Shock Transcription Factor HSF1 Activation by HSP90 (HSP90 Complex) that Forms a Stress-Sensitive Complex with HSF1

1998 • 1,198 citations

Mechanisms of Muscle Wasting — The Role of the Ubiquitin–Proteasome Pathway

1996 • 1,149 citations

Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease

2000 • 1,063 citations

Role of Oxidants in Ischemic Brain Damage

1996 • 1,037 citations

Role of the Human Heat Shock Protein hsp70 in Protection against Stress-Induced Apoptosis

1997 • 961 citations

Ataxin-1 Nuclear Localization and Aggregation

1998 • 959 citations

THE MAINTENANCE OF THE ACCURACY OF PROTEIN SYNTHESIS AND ITS RELEVANCE TO AGEING

1963 • 950 citations

A Receptor for the Selective Uptake and Degradation of Proteins by Lysosomes

1996 • 904 citations

Abnormal Proteins Serve as Eukaryotic Stress Signals and Trigger the Activation of Heat Shock Genes

1986 • 904 citations

The Jnk1 and Jnk2 Protein Kinases Are Required for Regional Specific Apoptosis during Early Brain Development

1999 • 888 citations

Protein disaggregation mediated by heat-shock protein Hspl04

1994 • 861 citations

The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses

1987 • 850 citations

Degradation of oxidized proteins in mammalian cells

1997 • 845 citations

Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70

1999 • 830 citations

Negative regulation of the Apaf-1 apoptosome by Hsp70

2000 • 819 citations

Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1

1998 • 730 citations

Functional Role of Caspase-1 and Caspase-3 in an ALS Transgenic Mouse Model

2000 • 700 citations

Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils

2000 • 664 citations

Identification of genes that modify ataxin-1-induced neurodegeneration

2000 • 659 citations

Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease

1999 • 641 citations

Molecularchaperones as HSF1-specific transcriptional repressors

1998 • 623 citations

Support for the Prion Hypothesis for Inheritance of a Phenotypic Trait in Yeast

1996 • 620 citations

Formation of high molecular weight complexes of mutant Cu,Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis

2000 • 604 citations

Characterization and Dynamics of Aggresome Formation by a Cytosolic Gfp-Chimera✪

1999 • 592 citations

Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract

1996 • 580 citations

Caspase Cleavage of Gene Products Associated with Triplet Expansion Disorders Generates Truncated Fragments Containing the Polyglutamine Tract

1998 • 569 citations

The Sizes of Peptides Generated from Protein by Mammalian 26 and 20 S Proteasomes

1999 • 565 citations

Genetic Suppression of Polyglutamine Toxicity in Drosophila

2000 • 562 citations

Frameshift Mutants of β Amyloid Precursor Protein and Ubiquitin-B in Alzheimer's and Down Patients

1998 • 558 citations

Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins

2000 • 549 citations

MEKK1/JNK signaling stabilizes and activates p53

1998 • 521 citations

Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response

1999 • 521 citations

Production of abnormal proteins in E. coli stimulates transcription of ion and other heat shock genes

1985 • 521 citations

Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins.

1990 • 520 citations

Hsp70 Prevents Activation of Stress Kinases

1997 • 516 citations

Dynamic Association of Proteasomal Machinery with the Centrosome

1999 • 515 citations

Mutation of the E6-AP Ubiquitin Ligase Reduces Nuclear Inclusion Frequency While Accelerating Polyglutamine-Induced Pathology in SCA1 Mice

1999 • 507 citations

Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice

1999 • 505 citations

Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates

1998 • 490 citations

The base of the proteasome regulatory particle exhibits chaperone-like activity

1999 • 485 citations

Proteasome Inhibition Leads to a Heat-shock Response, Induction of Endoplasmic Reticulum Chaperones, and Thermotolerance

1997 • 464 citations

The Ubiquitin-Proteasome Pathway and Pathogenesis of Human Diseases

1999 • 459 citations

Translocation of SAPK/JNK to Mitochondria and Interaction with Bcl-xL in Response to DNA Damage

2000 • 421 citations

Analysis of the Role of Heat Shock Protein (Hsp) Molecular Chaperones in Polyglutamine Disease

1999 • 419 citations

Caspase-8 Is Required for Cell Death Induced by Expanded Polyglutamine Repeats

1999 • 418 citations

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm

1994 • 415 citations

Degradation of α-Synuclein by Proteasome

1999 • 406 citations

Biosynthesis and Degradation of CFTR

1999 • 406 citations

Evidence for Proteasome Involvement in Polyglutamine Disease: Localization to Nuclear Inclusions in SCA3/MJD and Suppression of Polyglutamine Aggregation in vitro

1999 • 406 citations

Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders.

1998 • 403 citations

Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture

1998 • 376 citations

Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans

2000 • 366 citations

Huntingtin Is Ubiquitinated and Interacts with a Specific Ubiquitin-conjugating Enzyme

1996 • 365 citations

Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease

2000 • 360 citations

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch

1998 • 360 citations

Ubiquitin C-Terminal Hydrolase Is an Immediate-Early Gene Essential for Long-Term Facilitation in Aplysia

1997 • 359 citations

Glutamine Repeats and Neurodegenerative Diseases: Molecular Aspects

2002 • 354 citations

Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis

1999 • 338 citations

Stress-Inducible Cellular Responses

1995 • 337 citations

PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone

2000 • 330 citations

Chaperones Hsp70 and Hsp40 Suppress Aggregate Formation and Apoptosis in Cultured Neuronal Cells Expressing Truncated Androgen Receptor Protein with Expanded Polyglutamine Tract

2000 • 314 citations

Induction of thermotolerance and enhanced heat shock protein synthesis in chinese hamster fibroblasts by sodium arsenite and by ethanol

1983 • 306 citations

Proteasome Inhibitors Activate Stress Kinases and Induce Hsp72

1998 • 304 citations

Heat shock proteins: regulators of stress response and apoptosis

1998 • 300 citations

Ubiquitin-dependent Degradation of Certain Protein Substrates in Vitro Requires the Molecular Chaperone Hsc70

1997 • 294 citations

Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron

1999 • 289 citations

Proteasome Active Sites Allosterically Regulate Each Other, Suggesting a Cyclical Bite-Chew Mechanism for Protein Breakdown

1999 • 282 citations

Overexpression of peptide-methionine sulfoxide reductase inSaccharomyces cerevisiaeand human T cells provides them with high resistance to oxidative stress

1998 • 268 citations

Up‐Regulation of Protein Chaperones Preserves Viability of Cells Expressing Toxic Cu/Zn‐Superoxide Dismutase Mutants Associated with Amyotrophic Lateral Sclerosis

1999 • 262 citations

INTRACELLULAR SIGNALING FROM THE ENDOPLASMIC RETICULUM TO THE NUCLEUS

1998 • 258 citations

Decrease in Peptide Methionine Sulfoxide Reductase in Alzheimer's Disease Brain

1999 • 251 citations

Principles of Chaperone-Assisted Protein Folding: Differences Between in Vitro and in Vivo Mechanisms

1996 • 249 citations

Antagonistic Interactions between Yeast Chaperones Hsp104 and Hsp70 in Prion Curing

1999 • 245 citations

Role of Hsp70 in regulation of stress‐kinase JNK: implications in apoptosis and aging

1998 • 240 citations

Protein-Damaging Stresses Activate c-Jun N-Terminal Kinase via Inhibition of Its Dephosphorylation: a Novel Pathway Controlled by HSP72

1999 • 239 citations

The c-Jun N-Terminal Kinase Cascade Plays a Role in Stress-Induced Apoptosis in Jurkat Cells by Up-Regulating Fas Ligand Expression

1998 • 238 citations

Size-dependent Disaggregation of Stable Protein Aggregates by the DnaK Chaperone Machinery

2000 • 226 citations

Proteasome Inhibitors Cause Induction of Heat Shock Proteins and Trehalose, Which Together Confer Thermotolerance in Saccharomyces cerevisiae

1998 • 226 citations

From Charcot to SOD1

1999 • 224 citations

Aging-associated Changes in Human Brain

1997 • 218 citations

Intracellular Localization of Proteasomal Degradation of a Viral Antigen

1999 • 214 citations

Immunocytochemical Co-localization of the Proteasome in Ubiquitinated Structures in Neurodegenerative Diseases and the Elderly

1997 • 214 citations

The cellular response to protein misfolding in the endoplasmic reticulum.

1999 • 210 citations

Lysosomes, a meeting point of proteins, chaperones, and proteases

1997 • 201 citations

Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: Relevance to diseases of the nervous system

1996 • 200 citations

Transglutaminase Action Imitates Huntington's Disease: Selective Polymerization of Huntingtin Containing Expanded Polyglutamine

1998 • 200 citations

Expression of Alzheimer’s Disease-associated Presenilin-1 Is Controlled by Proteolytic Degradation and Complex Formation

1998 • 199 citations

Stress-Induced Fas Ligand Expression in T Cells Is Mediated through a MEK Kinase 1-Regulated Response Element in the Fas Ligand Promoter

1998 • 193 citations

Recognition of Misfolding Proteins by PA700, the Regulatory Subcomplex of the 26 S Proteasome

2000 • 191 citations

Alpha synuclein in neurodegenerative disorders: Murderer or accomplice?

1998 • 190 citations

Thermotolerance in mammalian cells protein denaturation and aggregation, and stress proteins

1993 • 188 citations

Roles of molecular chaperones in protein degradation.

1996 • 186 citations

Denatured hemoglobin in sickle erythrocytes.

1977 • 185 citations

CAG expansion affects the expression of mutant huntingtin in the Huntington's disease brain

1995 • 180 citations

The DnaK chaperone modulates the heat shock response of Escherichia coli by binding to the sigma 32 transcription factor.

1992 • 178 citations

Activity and Regulation of the Centrosome-associated Proteasome

2000 • 172 citations

The Transcriptional regulation of heat shock genes: A plethora of heat shock factors and regulatory conditions

1996 • 170 citations

Protein Folding In Vivo: Unraveling Complex Pathways

1997 • 170 citations

Untitled

1998 • 168 citations

Hsp72-Mediated Suppression of c-Jun N-Terminal Kinase Is Implicated in Development of Tolerance to Caspase-Independent Cell Death

2000 • 161 citations

Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin.

1996 • 159 citations

Involvement of the Molecular Chaperone Ydj1 in the Ubiquitin-Dependent Degradation of Short-Lived and Abnormal Proteins in Saccharomyces cerevisiae

1996 • 153 citations

Induced thermotolerance to apoptosis in a human T lymphocyte cell line

1992 • 149 citations

Cellular adaptation in metal toxicology and metallothionein

1983 • 149 citations

Degradation of abnormal proteins in Escherichia coli. Formation of protein inclusions in cells exposed to amino acid analogs.

1975 • 148 citations

The stress gene response in brain.

1996 • 143 citations

Evidence for a role of Hsp 70 in the regulation of the heat shock response in mammalian cells

1996 • 141 citations

Chromosomal localization of the mammalian peptide-methionine sulfoxide reductase gene and its differential expression in various tissues.

1996 • 132 citations

Diminished heat shock response in the aged myocardium

1996 • 131 citations

Expression of Polyglutamine-expanded Huntingtin Activates the SEK1-JNK Pathway and Induces Apoptosis in a Hippocampal Neuronal Cell Line

1998 • 128 citations

Thermal Protein Denaturation and Protein Aggregation in Cells Made Thermotolerant by Various Chemicals: Role of Heat Shock Proteins

1995 • 128 citations

How do intracellular proteolytic systems change with age

1998 • 120 citations

Hsp70 and aging

1994 • 119 citations

Mechanisms of kidney cell injury from metals.

1993 • 118 citations

Oxidative stress, mutant SOD1, and neurofilament pathology in transgenic mouse models of human motor neuron disease.

1997 • 113 citations

Evidence That Endoplasmic Reticulum (ER)-associated Degradation of Cystic Fibrosis Transmembrane Conductance Regulator Is Linked to Retrograde Translocation from the ER Membrane

1999 • 112 citations

Ca2+-free Calmodulin and Calmodulin Damaged byin Vitro Aging Are Selectively Degraded by 26 S Proteasomes without Ubiquitination

2000 • 109 citations

Cleavage of Atrophin-1 at Caspase Site Aspartic Acid 109 Modulates Cytotoxicity

1999 • 108 citations

ICE, neuronal apoptosis and neurodegeneration

1998 • 105 citations

Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA)

1999 • 105 citations

Cellular and molecular mechanisms of aging

1993 • 102 citations

Age-related Decline in Ubiquitin Conjugation in Response to Oxidative Stress in the Lens

1997 • 97 citations

The Ligation Systems for Ubiquitin and Ubiquitin-like Proteins

1998 • 97 citations

Caspase activation during apoptotic cell death induced by expanded polyglutamine in N2a cells

1999 • 96 citations

Polyglutamine Domains Are Substrates of Tissue Transglutaminase: Does Transglutaminase Play a Role in Expanded CAG/Poly‐Q Neurodegenerative Diseases?

1997 • 92 citations

Scrapie prions selectively modify the stress response in neuroblastoma cells.

1995 • 88 citations

Sensing stress and responding to stress

1996 • 87 citations

Heat-shock-induced denaturation of proteins. Characterization of the insolubilization of the interferon-induced p68 kinase

1991 • 83 citations

Reevaluation of the Role of de Novo Protein Synthesis in Rat Thymocyte Apoptosis

1995 • 82 citations

The Function of HSP72 in Suppression of c-Jun N-terminal Kinase Activation Can Be Dissociated from Its Role in Prevention of Protein Damage

1999 • 81 citations

Maintenance and inheritance of yeast prions

1996 • 77 citations

Progress in pathogenesis studies of spinocerebellar ataxia type 1

1999 • 77 citations

Huntingtin: a single bait hooks many species

1998 • 74 citations

Caspase-3 Cleaves the Expanded Androgen Receptor Protein of Spinal and Bulbar Muscular Atrophy in a Polyglutamine Repeat Length-Dependent Manner

1998 • 73 citations

Involvement of molecular chaperones in intracellular protein breakdown

1996 • 72 citations

Transgenic Mice in the Study of Polyglutamine Repeat Expansion Diseases

1998 • 72 citations

Toward Understanding the Molecular Pathology of Huntington's Disease

1997 • 72 citations

The induction of stress-related proteins by lead.

1986 • 68 citations

Regulation of expanded polyglutamine protein aggregation and nuclear localization by the glucocorticoid receptor

2000 • 67 citations

Glutathione, oxidative stress and aging

1996 • 67 citations

Triggering of neuronal cell death by accumulation of activated SEK1 on nuclear polyglutamine aggregations in PML bodies

1999 • 64 citations

Heat shock causes protein aggregation and reduced protein solubility at the centrosome and other cytoplasmic locations

1996 • 55 citations

Altered cellular responsiveness during ageing

1991 • 54 citations

Implications of heat shock/stress proteins for medicine and disease.

1998 • 54 citations

Inclusion body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta 114

1988 • 53 citations

Dual Roles of Proteasome in the Metabolism of Presenilin 1

1999 • 49 citations

Reduced thermotolerance in aged cells results from a loss of an hsp72- mediated control of JNK signaling pathway

1998 • 48 citations

Inclusion body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta 114

1988 • 47 citations

Endosome-Lysosomes, Ubiquitin and Neurodegeneration

1996 • 47 citations

Free radical and oxidative damage in human blood cells

1997 • 46 citations

Properties of abnormal proteins degraded rapidly in reticulocytes. Intracellular aggregation of the globin molecules prior to hydrolysis.

1981 • 45 citations

Protein aggregation and inclusion body formation in Escherichia coli rpoH mutant defective in heat shock protein induction

1991 • 44 citations

Modulation of intracellular protein degradation by SSB1–SIS1 chaperon system in yeast S. cerevisiae

1997 • 42 citations

Expression of Extended Polyglutamine Sequentially Activates Initiator and Effector Caspases

1999 • 41 citations

Glutamine repeats and neurodegenerative diseases

1999 • 37 citations

Skein-like inclusions in the neostriatum from a case of amyotrophic lateral sclerosis with dementia

1998 • 37 citations

Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation

1999 • 36 citations

UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is a heat shock gene that is also subject to catabolite derepression control

1997 • 34 citations

Overexpression of bacterial hemoglobin causes incorporation of pre-beta-lactamase into cytoplasmic inclusion bodies

1993 • 33 citations

Age-related decrease in the inductability of heat shock protein 72 in normal human skin

1996 • 31 citations

Role of catalase and heat shock protein on recovery of cardiac endothelial and mechanical function after ischemia.

1993 • 30 citations

Induction of Heat-Shock Protein Synthesis and Thermotolerance in EL-4 Ascites Tumor Cells by Transient ATP Depletion after Ischemic Stress

1994 • 29 citations

C-Terminal Maturation Fragments of Presenilin 1 and 2 Control Secretion of APPα and Aβ by Human Cells and Are Degraded by Proteasome

1999 • 29 citations

Modeling protein homopolymeric repeats: possible polyglutamine structural motifs for Huntington's disease.

1998 • 26 citations

HLA-DR Chains Enter into an Aggregated Complex Containing GRP-78/BiP Prior to Their Degradation by the Pre-Golgi Degradative Pathway

1995 • 25 citations

Thermotolerance and the heat shock proteins.

1987 • 23 citations

The Younger Dryas: Cold, Cold Everywhere?

2000 • 23 citations

Genetic analysis of ubiquitin-dependent protein degradation

1992 • 19 citations

Thermotolerance and the heat shock proteins.

1987 • 19 citations

Transglutaminase as the agent of neurodegenerative diseases due to polyglutamine expansion.

1998 • 13 citations

Puromycin Induces Apoptosis of Developing Chick Sympathetic Neurons in a Similar Manner to NGF-deprivation

1995 • 13 citations

Mad cows meet mad yeast: the prion hypothesis.

1996 • 9 citations