Oxidative and Electrophilic Stresses Activate Nrf2 through Inhibition of Ubiquitination Activity of Keap1

THE UBIQUITIN SYSTEM

1998 • 8,360 citations

Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain

1999 • 3,344 citations

Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2

2004 • 2,037 citations

Function and regulation of cullin–RING ubiquitin ligases

2005 • 2,024 citations

Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants

2002 • 1,849 citations

Nrf2–Keap1 defines a physiologically important stress response mechanism

2004 • 1,618 citations

Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex

2002 • 1,442 citations

Distinct Cysteine Residues in Keap1 Are Required for Keap1-Dependent Ubiquitination of Nrf2 and for Stabilization of Nrf2 by Chemopreventive Agents and Oxidative Stress

2003 • 1,353 citations

Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element

2003 • 1,204 citations

Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex

2004 • 1,180 citations

Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell Survival

2003 • 1,140 citations

HIF-1 and mechanisms of hypoxia sensing

2001 • 1,131 citations

Keap1-dependent Proteasomal Degradation of Transcription Factor Nrf2 Contributes to the Negative Regulation of Antioxidant Response Element-driven Gene Expression

2003 • 1,065 citations

The SCF ubiquitin ligase: insights into a molecular machine

2004 • 1,059 citations

Molecular Mechanisms Activating the Nrf2-Keap1 Pathway of Antioxidant Gene Regulation

2005 • 1,033 citations

Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53

2000 • 1,026 citations

Protection against electrophile and oxidant stress by induction of the phase 2 response: Fate of cysteines of the Keap1 sensor modified by inducers

2004 • 948 citations

The Keap1-BTB Protein Is an Adaptor That Bridges Nrf2 to a Cul3-Based E3 Ligase: Oxidative Stress Sensing by a Cul3-Keap1 Ligase

2004 • 919 citations

Role ofVHLGene Mutation in Human Cancer

2004 • 910 citations

Keap1 regulates both cytoplasmic‐nuclear shuttling and degradation of Nrf2 in response to electrophiles

2003 • 791 citations

BTB Protein Keap1 Targets Antioxidant Transcription Factor Nrf2 for Ubiquitination by the Cullin 3-Roc1 Ligase

2004 • 701 citations

PERK-dependent Activation of Nrf2 Contributes to Redox Homeostasis and Cell Survival following Endoplasmic Reticulum Stress

2004 • 691 citations

Increased Protein Stability as a Mechanism That Enhances Nrf2-mediated Transcriptional Activation of the Antioxidant Response Element

2003 • 587 citations

Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups

2001 • 568 citations

Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products

2004 • 561 citations

Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes

2004 • 504 citations

A hitchhiker's guide to the cullin ubiquitin ligases: SCF and its kin

2004 • 455 citations

Degradation of Transcription Factor Nrf2 via the Ubiquitin-Proteasome Pathway and Stabilization by Cadmium

2003 • 447 citations

Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ^12,14-Prostaglandin J₂

2003 • 395 citations

Ubiquitin Enters the New Millennium

2001 • 390 citations

Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells

1999 • 388 citations

Redox-regulated Turnover of Nrf2 Is Determined by at Least Two Separate Protein Domains, the Redox-sensitive Neh2 Degron and the Redox-insensitive Neh6 Degron

2004 • 381 citations

The Keap1 BTB/POZ Dimerization Function Is Required to Sequester Nrf2 in Cytoplasm

2002 • 340 citations

Chemoprevention through the Keap1–Nrf2 signaling pathway by phase 2 enzyme inducers

2004 • 309 citations

CAND1 Binds to Unneddylated CUL1 and Regulates the Formation of SCF Ubiquitin E3 Ligase Complex

2002 • 302 citations

Covalent modification of all members of human cullin family proteins by NEDD8

1999 • 295 citations

Unique Function of the Nrf2–Keap1 Pathway in the Inducible Expression of Antioxidant and Detoxifying Enzymes

2004 • 236 citations

Keap1, the Sensor for Electrophiles and Oxidants that Regulates the Phase 2 Response, Is a Zinc Metalloprotein

2005 • 210 citations

Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome

2004 • 203 citations

The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases?

2003 • 186 citations

Neddylation and Deneddylation of CUL-3 Is Required to Target MEI-1/Katanin for Degradation at the Meiosis-to-Mitosis Transition in C. elegans

2003 • 176 citations

Thioredoxin as a Molecular Target of Cyclopentenone Prostaglandins

2003 • 167 citations

NF-κB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach

2003 • 152 citations

Protection against electrophile and oxidative stress by induction of phase 2 genes: the quest for the elusive sensor that responds to inducers

2004 • 142 citations

RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex

2004 • 121 citations

Inducible dissociation of SCFMet30 ubiquitin ligase mediates a rapid transcriptional response to cadmium

2005 • 81 citations

Cullin 3 Promotes Proteasomal Degradation of the Topoisomerase I-DNA Covalent Complex

2004 • 68 citations

Inhibition of the 26S Proteasome Induces Expression of GLCLC, the Catalytic Subunit for γ-Glutamylcysteine Synthetase

2000 • 49 citations

Observations on metabolism of C14-diethylstilbestrol

1951 • 5 citations